Cytomegalovirus infection in inflammatory bowel disease is not associated with worsening of intestinal inflammatory activity.

PubMed

do Carmo, Alexandre Medeiros; Santos, Fabiana Maria; Ortiz-Agostinho, Carmen Lucia; Nishitokukado, Iêda; Frota, Cintia S; Gomes, Flavia Ubeda; Leite, André Zonetti de Arruda; Pannuti, Claudio Sérgio; Boas, Lucy Santos Vilas; Teixeira, Magaly Gemio; Sipahi, Aytan Miranda

2014-01-01

Cytomegalovirus is highly prevalent virus and usually occurs in immunocompromised patients. The pathophysiology and treatment of inflammatory bowel disease often induce a state of immunosuppression. Because this, there are still doubts and controversies about the relationship between inflammatory bowel disease and cytomegalovirus. Evaluate the frequency of cytomegalovirus in patients with inflammatory bowel disease and identify correlations. Patients with inflammatory bowel disease underwent an interview, review of records and collection of blood and fecal samples. The search for cytomegalovirus was performed by IgG and IgM blood serology, by real-time PCR in the blood and by qualitative PCR in feces. Results were correlated with red blood cell levels, C-reactive protein levels, erythrocyte sedimentation rates and fecal calprotectin levels for each patient. Among the 400 eligible patients, 249 had Crohn's disease, and 151 had ulcerative colitis. In the group of Crohn's disease, 67 of the patients had moderate or severe disease, but 126 patients presented with active disease, based on the evaluation of the fecal calprotectin. In patients with ulcerative colitis, only 21 patients had moderate disease, but 76 patients presented with active disease, based on the evaluation of the fecal calprotectin. A large majority of patients had positive CMV IgG. Overall, 10 patients had positive CMV IgM, and 9 patients had a positive qualitative detection of CMV DNA by PCR in the feces. All 400 patients returned negative results after the quantitative detection of CMV DNA in blood by real-time PCR. Analyzing the 19 patients with active infections, we only found that such an association occurred with the use of combined therapy (anti-TNF-alpha + azathioprine). The findings show that latent cytomegalovirus infections are frequent and active cytomegalovirus infection is rare. We did not find any association between an active infection of CMV and inflammatory bowel disease activity.

Inflammatory markers in relation to body composition, physical activity and assessment of nutritional status of the adolescents.

PubMed

Neves Miranda, Valter Paulo; Gouveia Peluzio, Maria do Carmo; Rodrigues de Faria, Eliana; Castro Franceschini, Sylvia do Carmo; Eloiza Priore, Silvia

2015-05-01

The evaluation of inflammatory markers during adolescence can monitor different stages and manifestation of chronic diseases in adulthood. The control of the subclinical inflammation process through changes in lifestyle, especially in the practice of physical activity and dietary education can mitigate the effects of risk factors that trigger the process of atherosclerosis. To do a critical review regarding inflammatory markers as a risk factor of cardiovascular disease in relation to body composition, physical activity and assessment of nutritional status of adolescents. A literature review was performed in the following electronic databases: PUBMED, SCIELO and CONCHRANE COLLECTION. The following associated terms were used "inflammation AND cardiovascular diseases AND nutritional status OR body composition OR physical activity". There were topics created for the discussion of subjects: obesity and risk factors for cardiovascular disease during adolescence; expression of inflammatory markers in adolescence; development of cardiovascular disease with inflammatory markers, and finally, inflammatory markers, physical activity and nutritional evaluation. It was observed that the inflammatory markers may manifest in adolescence and be related to risk factors for cardiovascular diseases. Physical activity and nutritional evaluation featured as non-pharmacological measures to control the incidence of inflammatory markers and cardiovascular risk factor. Intervention studies may clarify how the adoption of a more proper lifestyle can influence the inflammatory process. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Evaluation of QT and P wave dispersion and mean platelet volume among inflammatory bowel disease patients.

PubMed

Dogan, Yuksel; Soylu, Aliye; Eren, Gulay A; Poturoglu, Sule; Dolapcioglu, Can; Sonmez, Kenan; Duman, Habibe; Sevindir, Isa

2011-01-01

In inflammatory bowel disease (IBD) number of thromboembolic events are increased due to hypercoagulupathy and platelet activation. Increases in mean platelet volume (MPV) can lead to platelet activation, this leads to thromboembolic events and can cause acute coronary syndromes. In IBD patients, QT-dispersion and P-wave dispersion are predictors of ventricular arrhythmias and atrial fibrilation; MPV is accepted as a risk factor for acute coronary syndromes, we aimed at evaluating the correlations of these with the duration of disease, its localization and activity. The study group consisted of 69 IBD (Ulcerative colitis n: 54, Crohn's Disease n: 15) patients and the control group included 38 healthy individuals. Disease activity was evaluated both endoscopically and clinically. Patients with existing cardiac conditions, those using QT prolonging medications and having systemic diseases, anemia and electrolyte imbalances were excluded from the study. QT-dispersion, P-wave dispersion and MPV values of both groups were compared with disease activity, its localization, duration of disease and the antibiotics used. The P-wave dispersion values of the study group were significantly higher than those of the control group. Duration of the disease was not associated with QT-dispersion, and MPV levels. QT-dispersion, P-wave dispersion, MPV and platelet count levels were similar between the active and in mild ulcerative colitis patients. QT-dispersion levels were similar between IBD patients and the control group. No difference was observed between P-wave dispersion, QT-dispersion and MPV values; with regards to disease duration, disease activity, and localization in the study group (p>0.05). P-wave dispersion which is accepted as a risk factor for the development of atrial fibirilation was found to be high in our IBD patients. This demonstrates us that the risk of developing atrial fibrillation may be high in patients with IBD. No significant difference was found in the QT-dispersion, and in the MPV values when compared to the control group.

Correlation of rheumatoid arthritis activity indexes (Disease Activity Score 28 measured with ESR and CRP, Simplified Disease Activity Index and Clinical Disease Activity Index) and agreement of disease activity states with various cut-off points in a Northeastern Brazilian population.

PubMed

Medeiros, Marta Maria das Chagas; de Oliveira, Brenda Maria Gurgel Barreto; de Cerqueira, João Victor Medeiros; Quixadá, Raquel Telles de Souza; de Oliveira, Ídila Mont'Alverne Xavier

2015-01-01

The Disease Activity Score 28 (DAS28) and its versions have been used to measure rheumatoid arthritis (RA) activity, but there is no consensus about which one is the best. Determine the correlation among indexes (DAS28 ESR, DAS28 CRP, SDAI and CDAI) and evaluate agreement of activity strata using different cutoff points. Rheumatoid arthritis patients were cross-sectionally evaluated with data collection to calculate the DAS28 (ESR and CRP), SDAI and CDAI, using different cut-offs for defining remission, mild, moderate and high activity. Pearson correlations were calculated for continuous measures and agreement (kappa test) for the strata (remission, mild, moderate and high activity). Of 111 patients included, 108 were women, age 55.6 years, 11-year disease duration. DAS28 (ESR) was significantly higher than DAS28 (CRP) (4.0 vs. 3.5; p<0.001) and the values remained higher after stratification by age, gender, disease duration, rheumatoid factor and HAQ. Correlations among indexes ranged from 0.84 to 0.99, with better correlation between SDAI and CDAI. Agreements among activity strata ranged from 46.8% to 95.8%. DAS28 (CRP) with cut-off point for the remission of 2.3 underestimated disease activity by 45.8% compared with DAS28 (ESR). SDAI and CDAI showed agreement of 95.8%. The four indexes were associated with disease duration and HAQ. Although the activity indexes show good correlation, they show discrepancies in activity strata, thus requiring more researches to define a better index and better cutoff points. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

A conceptual framework for the evaluation of HLB surveillance activities.

USDA-ARS?s Scientific Manuscript database

Surveillance activities play an integral part in disease prevention and control, and underpin the three main stages of disease mitigation: the prevention of entry and establishment of exotic pathogens; the detailed investigation of more established pathogens; and the monitoring of disease control me...

Cost effectiveness of community-based physical activity interventions.

PubMed

Roux, Larissa; Pratt, Michael; Tengs, Tammy O; Yore, Michelle M; Yanagawa, Teri L; Van Den Bos, Jill; Rutt, Candace; Brownson, Ross C; Powell, Kenneth E; Heath, Gregory; Kohl, Harold W; Teutsch, Steven; Cawley, John; Lee, I-Min; West, Linda; Buchner, David M

2008-12-01

Physical inactivity is associated with the increased risk of many chronic diseases. Such risks decrease with increases in physical activity. This study assessed the cost-effectiveness of population-wide strategies to promote physical activity in adults and followed disease incidence over a lifetime. A lifetime cost-effectiveness analysis from a societal perspective was conducted to estimate the costs, health gains, and cost-effectiveness (dollars per quality-adjusted life year [QALY] gained, relative to no intervention) of seven public health interventions to promote physical activity in a simulated cohort of healthy U.S. adults stratified by age, gender, and physical activity level. Interventions exemplifying each of four strategies strongly recommended by the Task Force on Community Preventive Services were evaluated: community-wide campaigns, individually adapted health behavior change, community social-support interventions, and the creation of or enhanced access to physical activity information and opportunities. Each intervention was compared to a no-intervention alternative. A systematic review of disease burden by physical activity status was used to assess the relative risk of five diseases (coronary heart disease, ischemic stroke, type 2 diabetes, breast cancer, and colorectal cancer) across a spectrum of physical activity levels. Other data were obtained from clinical trials, population-based surveys, and other published literature. Cost-effectiveness ratios ranged between $14,000 and $69,000 per QALY gained, relative to no intervention. Results were sensitive to intervention-related costs and effect size. All of the evaluated physical activity interventions appeared to reduce disease incidence, to be cost-effective, and--compared with other well-accepted preventive strategies--to offer good value for money. The results support using any of the seven evaluated interventions as part of public health efforts to promote physical activity.

Evaluation of occupational allergic contact dermatitis and its related factors in Iran.

PubMed

Nassiri-Kashani, Mansour; Nassiri-Kashani, Mohammad Hassan; Ghafari, Mostafa

2016-01-01

Background: Occupational contact dermatitis, especially in hand, is one of the most common occupational disorders. The present study aimed at evaluating patients with occupational allergic contact dermatitis (ACD) caused by common allergens based on occupation type and disease history. Methods: This cross-sectional study aimed at evaluating the data of the patients with probable diagnosis of ACD in Center for Research and Training in Skin Diseases and Leprosy (CRTSDL) in Iran. In the present study, 946 patients were assessed from different regions of Iran. One hundred fifty-one cases with positive patch test and relevant exposure were entered into the study; data related to their occupation and disease activity history were evaluated and recorded. Then, factors related to disease activity history were assessed considering the occupational groups and common exposures. Results: Nickel sulphate was the most common allergen in the 151 patients. Disease activity was constant in 29.8% of the patients; it increased in 27.8%, and decreased just before doing the patch test in 42.4%. Of the patients, 52.3% were getting worse during the working days. Occupational groups were significantly different in age and gender. Disease duration was also different in the occupational groups (p=0.001). The least disease duration was observed in healthcare workers, and the most in service workers. Lesions in the foot were related to period of employment. In administrative work group, (teachers, technicians and housewives) disease activity was decreased in the most cases, while it was increased in most patients of service workers (p=0.086). Conclusion: The present study, similar to previous reports, revealed that nickel sulphate is the most common allergen in ACD cases. Moreover, it was found that the symptoms of disease activity remained constant or increased in a significant proportion of the cases during the working days. Therefore, these workers should seriously follow up on this matter and change their occupation, or limit the exposure to allergens.

An early and late peak in microglial activation in Alzheimer's disease trajectory.

PubMed

Fan, Zhen; Brooks, David J; Okello, Aren; Edison, Paul

2017-03-01

Amyloid-β deposition, neuroinflammation and tau tangle formation all play a significant role in Alzheimer's disease. We hypothesized that there is microglial activation early on in Alzheimer's disease trajectory, where in the initial phase, microglia may be trying to repair the damage, while later on in the disease these microglia could be ineffective and produce proinflammatory cytokines leading to progressive neuronal damage. In this longitudinal study, we have evaluated the temporal profile of microglial activation and its relationship between fibrillar amyloid load at baseline and follow-up in subjects with mild cognitive impairment, and this was compared with subjects with Alzheimer's disease. Thirty subjects (eight mild cognitive impairment, eight Alzheimer's disease and 14 controls) aged between 54 and 77 years underwent 11C-(R)PK11195, 11C-PIB positron emission tomography and magnetic resonance imaging scans. Patients were followed-up after 14 ± 4 months. Region of interest and Statistical Parametric Mapping analysis were used to determine longitudinal alterations. Single subject analysis was performed to evaluate the individualized pathological changes over time. Correlations between levels of microglial activation and amyloid deposition at a voxel level were assessed using Biological Parametric Mapping. We demonstrated that both baseline and follow-up microglial activation in the mild cognitive impairment cohort compared to controls were increased by 41% and 21%, respectively. There was a longitudinal reduction of 18% in microglial activation in mild cognitive impairment cohort over 14 months, which was associated with a mild elevation in fibrillar amyloid load. Cortical clusters of microglial activation and amyloid deposition spatially overlapped in the subjects with mild cognitive impairment. Baseline microglial activation was increased by 36% in Alzheimer's disease subjects compared with controls. Longitudinally, Alzheimer's disease subjects showed an increase in microglial activation. In conclusion, this is one of the first longitudinal positron emission tomography studies evaluating longitudinal changes in microglial activation in mild cognitive impairment and Alzheimer's disease subjects. We found there is an initial longitudinal reduction in microglial activation in subjects with mild cognitive impairment, while subjects with Alzheimer's disease showed an increase in microglial activation. This could reflect that activated microglia in mild cognitive impairment initially may adopt a protective activation phenotype, which later change to a cidal pro-inflammatory phenotype as disease progresses and amyloid clearance fails. Thus, we speculate that there might be two peaks of microglial activation in the Alzheimer's disease trajectory; an early protective peak and a later pro-inflammatory peak. If so, anti-microglial agents targeting the pro-inflammatory phenotype would be most beneficial in the later stages of the disease. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Pregnancy in systemic autoimmune diseases: Myths, certainties and doubts].

PubMed

Danza, Álvaro; Ruiz-Irastorza, Guillermo; Khamashta, Munther

2016-10-07

Systemic autoimmune diseases especially affect young women during childbearing age. The aim of this review is to update systemic lupus erythematosus, antiphospholipid syndrome and systemic sclerosis management during pregnancy. These diseases present variable maternal and fetal risks. Studies show that an appropriate disease control and a reasonable remission period prior to pregnancy are associated with satisfactory obstetric outcomes. Antiphospholipid autoantibodies profile, anti-Ro/anti-La antibodies, pulmonary pressure and activity evaluation are crucial to assess the pregnancy risk. Monitoring requires a multidisciplinary team, serial analytic controls and Doppler ultrasound of maternal and fetal circulation. Evaluation of the activity of the disease is essential. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

DWI at MR Enterography for Evaluating Bowel Inflammation in Crohn Disease.

PubMed

Park, Seong Ho

2016-07-01

The purpose of this article is to provide a comprehensive review regarding DWI enterography used for evaluating Crohn disease and to summarize the relevant evidence. Active bowel inflammation in Crohn disease causes restricted diffusion on MR enterography with DWI. Enterographic DWI to evaluate Crohn disease is increasingly drawing attention for both academic research and clinical practice and has shown potential as a quantitative tool for assessing bowel inflammation. DWI enterography also has multiple unresolved issues and limitations.

Validation of the Auto-Inflammatory Diseases Activity Index (AIDAI) for hereditary recurrent fever syndromes

PubMed Central

Piram, Maryam; Koné-Paut, Isabelle; Lachmann, Helen J; Frenkel, Joost; Ozen, Seza; Kuemmerle-Deschner, Jasmin; Stojanov, Silvia; Simon, Anna; Finetti, Martina; Sormani, Maria Pia; Martini, Alberto; Gattorno, Marco; Ruperto, Nicolino

2014-01-01

Objectives To validate the Auto-Inflammatory Diseases Activity Index (AIDAI) in the four major hereditary recurrent fever syndromes (HRFs): familial Mediterranean fever (FMF), mevalonate kinase deficiency (MKD), tumour necrosis factor receptor-associated periodic syndrome (TRAPS) and cryopyrin-associated periodic syndromes (CAPS). Methods In 2010, an international collaboration established the content of a disease activity tool for HRFs. Patients completed a 1-month prospective diary with 12 yes/no items before a clinical appointment during which their physician assessed their disease activity by a questionnaire. Eight international experts in auto-inflammatory diseases evaluated the patient's disease activity by a blinded web evaluation and a nominal group technique consensus conference, with their consensus judgement considered the gold standard. Sensitivity/specificity/accuracy measures and the ability of the score to discriminate active from inactive patients via the best cut-off score were calculated by a receiver operating characteristic analysis. Results Consensus was achieved for 98/106 (92%) cases (39 FMF, 35 CAPS, 14 TRAPS and 10 MKD), with 26 patients declared as having inactive disease and 72 as having active disease. The median total AIDAI score was 14 (range=0–175). An AIDAI cut-off score ≥9 discriminated active from inactive patients, with sensitivity/specificity/accuracy of 89%/92%/90%, respectively, and an area under the curve of 98% (95% CI 96% to 100%). Conclusions The AIDAI score is a valid and simple tool for assessing disease activity in FMF/MKD/TRAPS/CAPS. This tool is easy to use in clinical practice and has the potential to be used as the standard efficacy measure in future clinical trials. PMID:24026675

Lesional perfusion abnormalities in Leigh disease demonstrated by arterial spin labeling correlate with disease activity.

PubMed

Whitehead, Matthew T; Lee, Bonmyong; Gropman, Andrea

2016-08-01

Leigh disease is a metabolic disorder of the mitochondrial respiratory chain culminating in symmetrical necrotizing lesions in the deep gray nuclei or brainstem. Apart from classic gliotic/necrotic lesions, small-vessel proliferation is also characteristic on histopathology. We have observed lesional hyperperfusion on arterial spin-labeling (ASL) sequence in children with Leigh disease. In this cross-sectional analysis, we evaluated lesional ASL perfusion characteristics in children with Leigh syndrome. We searched the imaging database from an academic children's hospital for "arterial spin labeling, perfusion, necrosis, lactate, and Leigh" to build a cohort of children for retrospective analysis. We reviewed each child's medical record to confirm a diagnosis of Leigh disease, excluding exams with artifact, technical limitations, and without ASL images. We evaluated the degree and extent of cerebral blood flow and relationship to brain lesions. Images were compared to normal exams from an aged-matche cohort. The database search yielded 45 exams; 30 were excluded. We evaluated 15 exams from 8 children with Leigh disease and 15 age-matched normal exams. In general, Leigh brain perfusion ranged from hyperintense (n=10) to hypointense (n=5). Necrotic lesions appeared hypointense/hypoperfused. Active lesions with associated restricted diffusion demonstrated hyperperfusion. ASL perfusion patterns differed significantly from those on age-matched normal studies (P=<.0001). Disease activity positively correlated with cerebral deep gray nuclei hyperperfusion (P=0.0037) and lesion grade (P=0.0256). Children with Leigh disease have abnormal perfusion of brain lesions. Hyperperfusion can be found in active brain lesions, possibly associated with small-vessel proliferation characteristic of the disease.

Inflammatory bowel disease imaging: Current practice and future directions.

PubMed

Kilcoyne, Aoife; Kaplan, Jess L; Gee, Michael S

2016-01-21

The purpose of this paper is to evaluate the role of imaging in inflammatory bowel disease (IBD), including detection of extraluminal complications and extraintestinal manifestations of IBD, assessment of disease activity and treatment response, and discrimination of inflammatory from fibrotic strictures. IBD is a chronic idiopathic disease affecting the gastrointestinal tract that is comprised of two separate, but related intestinal disorders; Crohn's disease and ulcerative colitis. The paper discusses, in detail the pros and cons of the different IBD imaging modalities that need to be considered in order to optimize the imaging and clinical evaluation of patients with IBD. Historically, IBD evaluation of the bowel has included imaging to assess the portions of the small bowel that are inaccessible to optical endoscopic visualization. This traditionally was performed using barium fluoroscopic techniques; however, cross-sectional imaging techniques (computed tomography and magnetic resonance imaging) are being increasingly utilized for IBD evaluation because they can simultaneously assess mural and extramural IBD manifestations. Recent advances in imaging technology, that continue to improve the ability of imaging to noninvasively follow disease activity and treatment response, are also discussed. This review article summarizes the current imaging approach in inflammatory bowel disease as well as the role of emerging imaging modalities.

Assessing the activity of perianal Crohn's disease: comparison of clinical indices and computer-assisted anal ultrasound.

PubMed

Losco, Alessandra; Viganò, Chiara; Conte, Dario; Cesana, Bruno Mario; Basilisco, Guido

2009-05-01

Assessing perianal disease activity is important for the treatment and prognosis of Crohn's disease (CD) patients, but the diagnostic accuracy of the activity indices has not yet been established. The aim of this study was to determine the accuracy and agreement of the Fistula Drainage Assessment (FDA), Perianal Disease Activity Index (PDAI), and computer-assisted anal ultrasound imaging (AUS). Sixty-two consecutive patients with CD and perianal fistulae underwent clinical, FDA, PDAI, and AUS evaluation. Perianal disease was considered active in the presence of visible fistula drainage and/or signs of local inflammation (induration and pain at digital compression) upon clinical examination. The AUS images were analyzed by calculating the mean gray-scale tone of the lesion. The PDAI and gray-scale tone values discriminating active and inactive perianal disease were defined using receiver operating characteristics statistics. Perianal disease was active in 46 patients. The accuracy of the FDA was 87% (confidence interval [CI]: 76%-94%). A PDAI of >4 and a mean gray-scale tone value of 117 maximized sensitivity and specificity; their diagnostic accuracy was, respectively, 87% (CI: 76%-94%) and 81% (CI: 69%-90%). The agreement of the 3 evaluations was fair to moderate. The addition of AUS to the PDAI or FDA increased their diagnostic accuracy to respectively 95% and 98%. The diagnostic accuracy of the FDA, PDAI, and computer-assisted AUS imaging was good in assessing perianal disease activity in patients with CD. The agreement between the techniques was fair to moderate. Overall accuracy can be increased by combining the FDA or PDAI with AUS.

Increased inflammation and disease activity among current cigarette smokers with rheumatoid arthritis: a cross-sectional analysis of US veterans.

PubMed

Sokolove, Jeremy; Wagner, Catriona A; Lahey, Lauren J; Sayles, Harlan; Duryee, Michael J; Reimold, Andreas M; Kerr, Gail; Robinson, William H; Cannon, Grant W; Thiele, Geoffrey M; Mikuls, Ted R

2016-11-01

Cigarette smoking is a major risk factor for RA and has been associated with increased disease severity and lower rates of disease remission. We hypothesized that inflammation and disease activity would be associated with smoking status and this would be related to levels of ACPA. RA patients from the Veterans Affairs RA registry were studied (n = 1466): 76.9% anti-CCP2 positive, 89% male, median age 63 years (interquartile range 57-72), median disease duration 8.45 years (interquartile range 2.8-18). Baseline serum samples were evaluated for levels of anti-CCP2, RF, 19 distinct ACPAs and 17 cytokines. Smoking status at baseline was recorded as current, former or never. The association of smoking status with cytokines, autoantibodies and disease activity (DAS28) was evaluated. Among anti-CCP-positive RA patients, RA-associated cytokines (false-discovery rates q < 0.1%) and DAS28 (P < 0.01) were higher in current smokers compared with former or never smokers. DAS28 and cytokine levels were similar between former and never smokers. In contrast, ACPA concentrations were higher among both current and former smokers compared with never smokers, and levels of ACPA were not associated with DAS28 or cytokine levels. Among anti-CCP2-positive RA patients, current smoking status is associated with elevations in pro-inflammatory cytokines and increased RA disease activity. Similar levels of inflammation and disease activity among former and never smokers suggests that the detrimental effects of smoking could be ameliorated through tobacco cessation. The effect of tobacco cessation on RA disease activity should be evaluated prospectively. Published by Oxford University Press on behalf of the British Society for Rheumatology 2016. This work is written by US Government employees and is in the public domain in the United States.

Quality of Life in Swiss Paediatric Inflammatory Bowel Disease Patients: Do Patients and Their Parents Experience Disease in the Same Way?

PubMed

Mueller, Rebekka; Ziade, Farah; Pittet, Valérie; Fournier, Nicolas; Ezri, Jessica; Schoepfer, Alain; Schibli, Susanne; Spalinger, Johannes; Braegger, Christian; Nydegger, Andreas

2016-03-01

Inflammatory bowel diseases (IBDs) may impair quality of life (QoL) in paediatric patients. We aimed to evaluate in a nationwide cohort whether patients experience QoL in a different way when compared with their parents. Sociodemographic and psychosocial characteristics were prospectively acquired from paediatric patients and their parents included in the Swiss IBD Cohort Study. Disease activity was evaluated by the Paediatric Crohn's Disease Activity Index (PCDAI) and the Paediatric Ulcerative Colitis Activity Index (PUCAI). We assessed QoL using the KIDSCREEN questionnaire. The QoL domains were analysed and compared between children and parents according to type of disease, parents' age, origin, education and marital status. We included 110 children and parents (59 Crohn's disease [CD], 45 ulcerative colitis [UC], 6 IBD unclassified [IBDU]). There was no significant difference in QoL between CD and UC/IBDU, whether the disease was active or in remission. Parents perceived overall QoL, as well as 'mood', 'family' and 'friends' domains, lower than the children themselves, independently of their place of birth and education. However, better concordance was found on 'school performance' and 'physical activity' domains. Marital status and age of parents significantly influenced the evaluation of QoL. Mothers and fathers being married or cohabiting perceived significantly lower mood, family and friends domains than their children, whereas mothers living alone had a lower perception of the friends domain; fathers living alone had a lower perception of family and mood subscores. Parents of Swiss paediatric IBD patients significantly underestimate overall QoL and domains of QoL of their children independently of origin and education. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Diagnostic Testing and Interpretation of Tests for Autoimmunity

PubMed Central

Castro, Christine; Gourley, Mark

2010-01-01

Laboratory testing is of great value when evaluating a patient with a suspected autoimmune disease. The results can confirm a diagnosis, estimate disease severity, aid in assessing prognosis and are useful to follow disease activity. Components of the laboratory exam include complete blood count with differential, comprehensive metabolic panel, inflammatory markers, autoantibodies, and flow cytometry. This chapter discusses these components and includes a discussion about organ-specific immunologic diseases where immunological laboratory testing is employed. Comprehensive laboratory evaluation of a suspected autoimmune illness in conjunction with a thorough clinical evaluation provides a better understanding of a patient's immunologic disease. PMID:20061009

Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus: a cross-sectional study.

PubMed

Checa, A; Idborg, H; Zandian, A; Sar, D Garcia; Surowiec, I; Trygg, J; Svenungsson, E; Jakobsson, P-J; Nilsson, P; Gunnarsson, I; Wheelock, C E

2017-09-01

Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus. Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease. Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C 16:0 -ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C 16:0 -ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C 16:0 - and C 24:1 -hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment. Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated with disease activity. This study demonstrates the utility of simultaneously targeting multiple components of a pathway to establish disease associations.

Disease activity indices in coeliac disease: systematic review and recommendations for clinical trials.

PubMed

Hindryckx, Pieter; Levesque, Barrett G; Holvoet, Tom; Durand, Serina; Tang, Ceen-Ming; Parker, Claire; Khanna, Reena; Shackelton, Lisa M; D'Haens, Geert; Sandborn, William J; Feagan, Brian G; Lebwohl, Benjamin; Leffler, Daniel A; Jairath, Vipul

2018-01-01

Although several pharmacological agents have emerged as potential adjunctive therapies to a gluten-free diet for coeliac disease, there is currently no widely accepted measure of disease activity used in clinical trials. We conducted a systematic review of coeliac disease activity indices to evaluate their operating properties and potential as outcome measures in registration trials. MEDLINE, EMBASE and the Cochrane central library were searched from 1966 to 2015 for eligible studies in adult and/or paediatric patients with coeliac disease that included coeliac disease activity markers in their outcome measures. The operating characteristics of histological indices, patient-reported outcomes (PROs) and endoscopic indices were evaluated for content and construct validity, reliability, responsiveness and feasibility using guidelines proposed by the US Food and Drug Administration (FDA). Of 19 123 citations, 286 studies were eligible, including 24 randomised-controlled trials. Three of five PROs identified met most key evaluative criteria but only the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) have been approved by the FDA. All histological and endoscopic scores identified lacked content validity. Quantitative morphometric histological analysis had better reliability and responsiveness compared with qualitative scales. Endoscopic indices were infrequently used, and only one index demonstrated responsiveness to effective therapy. Current best evidence suggests that the CDSD and the CeD PRO are appropriate for use in the definition of primary end points in coeliac disease registration trials. Morphometric histology should be included as a key secondary or co-primary end point. Further work is needed to optimise end point configuration to inform efficient drug development. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Tocilizumab treatment leads to improvement in disease activity regardless of CCP status in rheumatoid arthritis.

PubMed

Cappelli, Laura C; Palmer, Judy Lynn; Kremer, Joel; Bingham, Clifton O

2017-10-01

Autoantibodies can be useful in predicting response to certain treatments in rheumatoid arthritis (RA). We aimed to evaluate initial response to tocilizumab (TCZ) by change in physician and patient-reported outcomes and laboratory parameters in a real-world cohort of patients with RA. We analyzed the data by autoantibody status to determine whether patients with seronegative RA had improved response to tocilizumab when compared to their seropositive counterparts. Data from the CORRONA RA registry were analyzed. Patients were included if they were started on TCZ and had data from a follow-up visit 4-8 months after initiation, as well as having information on serologic status. Serologic status was determined by presence of anti-cyclic citrullinated peptide (CCP) antibodies. Changes in disease activity measures from baseline to follow-up visit were evaluated. Both CCP-negative and -positive groups had statistically significant improvement in physician-reported measurements (physician rating of disease activity and joint counts), patient-reported measures (disease activity, pain, and fatigue), and acute phase reactants after 4-8 months of treatment with tocilizumab. The magnitude of improvement, however, did not differ significantly by CCP status. Tocilizumab led to statistically significant improvement in all patient- and physician-reported measures of disease activity evaluated in this cohort of patient with RA. The response to tocilizumab did not differ by CCP status. Copyright © 2017 Elsevier Inc. All rights reserved.

Monitoring and Evaluating the Ebola Response Effort in Two Liberian Communities.

PubMed

Munodawafa, Davison; Moeti, Matshidiso Rebecca; Phori, Peter Malekele; Fawcett, Stephen B; Hassaballa, Ithar; Sepers, Charles; Reed, Florence DiGennaro; Schultz, Jerry A; Chiriseri, Ephraim Tafadzwa

2018-04-01

Although credited with ultimately reducing incidence of Ebola Virus Disease (EVD) in West Africa, little is known about the amount and kind of Ebola response activities associated with reducing the incidence of EVD. Our team monitored Ebola response activities and associated effects in two rural counties in Liberia highly affected by Ebola. We used a participatory monitoring and evaluation system, and drew upon key informant interviews and document review, to systematically capture, code, characterize, and communicate patterns in Ebola response activities. We reviewed situation reports to obtain data on incidence of EVD over time. Results showed enhanced implementation of Ebola response activities corresponded with decreased incidence of EVD. The pattern of staggered implementation of activities and associated effects-replicated in both counties-is suggestive of the role of Ebola response activities in reducing EVD. Systematic monitoring of response activities to control disease outbreaks holds lessons for implementing and evaluating multi-sector, comprehensive community health efforts.

Circulating cathelicidin levels correlate with mucosal disease activity in ulcerative colitis, risk of intestinal stricture in Crohn's disease, and clinical prognosis in inflammatory bowel disease.

PubMed

Tran, Diana Hoang-Ngoc; Wang, Jiani; Ha, Christina; Ho, Wendy; Mattai, S Anjani; Oikonomopoulos, Angelos; Weiss, Guy; Lacey, Precious; Cheng, Michelle; Shieh, Christine; Mussatto, Caroline C; Ho, Samantha; Hommes, Daniel; Koon, Hon Wai

2017-05-12

Cathelicidin (LL-37) is an antimicrobial peptide known to be associated with various autoimmune diseases. We attempt to determine if cathelicidin can accurately reflect IBD disease activity. We hypothesize that serum cathelicidin correlates with mucosal disease activity, stricture, and clinical prognosis of IBD patients. Serum samples were collected from two separate cohorts of patients at the University of California, Los Angeles. Cohort 1 consisted of 50 control, 23 UC, and 28 CD patients. Cohort 2 consisted of 20 control, 57 UC, and 67 CD patients. LL-37 levels were determined by ELISA. Data from both cohorts were combined for calculation of accuracies in indicating mucosal disease activity, relative risks of stricture, and odds ratios of predicting disease development. Serum cathelicidin levels were inversely correlated with Partial Mayo Scores of UC patients and Harvey-Bradshaw Indices of CD patients. Among IBD patients with moderate or severe initial disease activity, the patients with high initial LL-37 levels had significantly better recovery than the patients with low initial LL-37 levels after 6-18 months, suggesting that high LL-37 levels correlate with good prognosis. Co-evaluation of LL-37 and CRP levels was more accurate than CRP alone or LL-37 alone in the correlation with Mayo Endoscopic Score of UC patients. Low LL-37 levels indicated a significantly elevated risk of intestinal stricture in CD patients. Co-evaluation of LL-37 and CRP can indicate mucosal disease activity in UC patients. LL-37 can predict future clinical activity in IBD patients and indicate risk of intestinal stricture in CD patients.

Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease.

PubMed

Meurs, Kathryn M; Olsen, Lisbeth H; Reimann, Maria J; Keene, Bruce W; Atkins, Clarke E; Adin, Darcy; Aona, Brent; Condit, Julia; DeFrancesco, Teresa; Reina-Doreste, Yamir; Stern, Joshua A; Tou, Sandra; Ward, Jessica; Woodruff, Kathleen

2018-02-01

Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is particularly common in the Cavalier King Charles Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin-converting enzyme inhibitors (ACE-I). We have previously identified a canine ACE gene polymorphism associated with a decrease in angiotensin-converting enzyme (ACE) activity. The aim of this study was to evaluate for the prevalence of the ACE polymorphism in CKCS with mitral valve disease and to determine whether the presence of the polymorphism is associated with alterations in ACE activity at different stages of cardiac disease. Seventy-three dogs with a diagnosis of mitral valve disease were evaluated and a blood sample was drawn for ACE polymorphism genotyping and ACE activity measurement. Forty-three dogs were homozygous for the ACE polymorphism; five were heterozygous and 25 were homozygous wild type. The mean age and the median severity of disease were not different for dogs with the polymorphism and dogs with the wild-type sequence. The median baseline ACE activity was significantly lower for the ACE polymorphism (27.0 U/l) than the wild-type sequence dogs (31.0 U/l) (P=0.02). Dogs with more severe disease and the ACE polymorphism had significantly lower levels of ACE activity than dogs with the wild-type sequence (P=0.03). The CKCS appears to have a high prevalence of the ACE variant. Dogs with the ACE variant had lower levels of ACE activity even in more advanced mitral valve disease than dogs without the variant. The clinical significance of this finding and its impact on the need for ACE-I in dogs with the polymorphism and heart disease deserves further study.

Evaluation of inflammatory activity in Crohn’s disease and ulcerative colitis

PubMed Central

Vilela, Eduardo Garcia; Torres, Henrique Osvaldo da Gama; Martins, Fabiana Paiva; Ferrari, Maria de Lourdes de Abreu; Andrade, Marcella Menezes; da Cunha, Aloísio Sales

2012-01-01

Crohn’s disease and ulcerative colitis evolve with a relapsing and remitting course. Determination of inflammatory state is crucial for the assessment of disease activity and for tailoring therapy. However, no simple diagnostic test for monitoring intestinal inflammation is available. Noninvasive markers give only indirect assessments of disease activity. Histopathological or endoscopical examinations accurately assess inflammatory activity, but they are invasive, time consuming and expensive and therefore are unsuitable for routine use. Imaging procedures are not applicable for ulcerative colitis. The usefulness of ultrasound and Doppler imaging in assessing disease activity is still a matter of discussion for Crohn’s disease, and an increased interest in computed tomography enterograph (CTE) has been seen, mainly because it can delineate the extent and severity of bowel wall inflammation, besides detecting extraluminal findings. Until now, the available data concerning the accuracy of magnetic resonance enterography in detecting disease activity is less than CTE. Due to this, clinical activity indices are still commonly used for both diseases. PMID:22408345

Evaluation of learned helplessness, self-efficacy and disease activity, functional capacity and pain in Argentinian patients with rheumatoid arthritis.

PubMed

Vergara, F; Rosa, J; Orozco, C; Bertiller, E; Gallardo, M A; Bravo, M; Catay, E; Collado, V; Gómez, G; Sabelli, M; García, M V; Rosemffet, M G; Citera, G; Schneeberger, E E; Catoggio, L J; Soriano, E R

2017-01-01

To evaluate the association between learned helplessness (LH) and self-efficacy (SE) with disease activity, functional capacity, and level of pain in patients with rheumatoid arthritis (RA) and to compare LH and SE between patients in remission and patients with active disease. This multicentre, cross-sectional study included consecutive patients (aged ≥ 18 years) with RA according to 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. LH was measured by the Rheumatology Attitude Index (RAI), Spanish version; SE with the Arthritis Self-efficacy Scale (ASES), Spanish version; functional capacity with the Health Assessment Questionnaire, Argentinian version (HAQ-A); and perceived pain by the visual analogue scale (VAS). Disease activity was measured by the Clinical Disease Activity Index (CDAI). A total of 115 patients (82% females) with a mean (± sd) age of 58 ± 13 years were included. We found a significantly positive correlation between LH and perceived pain (p < 0.001), HAQ-A score (p < 0.001), and CDAI (p < 0.001) and a significantly negative correlation between SE and perceived pain (p < 0.001), HAQ-A score (p < 0.001), and CDAI (p < 0.001). We found greater levels of SE and lower grades of LH in patients in remission compared to those with active disease (median 76 vs. 58; p < 0.001 and 6 vs. 11; p < 0.001, respectively). LH and SE correlated significantly with disease activity, functional capacity, and perceived pain. Levels of SE were higher in patients in remission compared to those with active disease as opposed to levels of LH, which were lower in patients in remission compared to those with active disease. These results show that cognitive factors are related to disease activity and their modifications may have importance in the management of RA.

Contrast-enhanced ultrasonography (CEUS) vs. MRI of the small bowel in the evaluation of Crohn's disease activity.

PubMed

Malagò, R; D'Onofrio, M; Mantovani, W; D'Alpaos, G; Foti, G; Pezzato, A; Caliari, G; Cusumano, D; Benini, L; Pozzi Mucelli, R

2012-03-01

The presence of disease activity in Crohn's disease (CD) is one of the main parameters used to establish whether optimal therapy should be drug therapy or surgery. However, a major problem in monitoring CD is the common mismatch between the patient's symptoms and imaging objective signs of disease activity. Bowel ultrasonography (US) has emerged as a low-cost, noninvasive technique in the diagnosis and follow-up of patients with CD. Accordingly, the use of contrast-enhanced US (CEUS) has made possible an evaluation of the vascular enhancement pattern, similar to the use of magnetic resonance imaging (MRI). The aim of our study was to evaluate the role of CEUS in comparison with small-bowel MRI for assessing Crohn's disease activity. We prospectively enrolled 30 consecutive patients with known CD. Clinical and laboratory data were compared with imaging findings obtained from MRI and CEUS of the small bowel. MRI was performed with a 1.5-T system using phased-array coils and biphasic orally administered contrast agent prior to and after gadolinium chelate administration. We performed US with a 7.5-MHz linear-array probe and a second-generation contrast agent. The parameters analysed in both techniques were the following: lesion length, wall thickness, layered wall appearance, comb sign, fibroadipose proliferation, presence of enlarged lymph nodes and stenosis. We classified parietal enhancement curves into two types in relation to the contrast pattern obtained with the time-intensity curves at MRI and CEUS: (1) quick washin, quick washout, (2) slow washin, plateau with a slow washout. Comparison between Crohn's disease activity index (CDAI) and MRI showed a low correlation, with an rho=0.398; correlation between CDAI-laboratory data and CEUS activity was low, with rho=0.354; correlation between MRI activity and CEUS activity was good, with rho = 0.791; high correlation was found between CEUS and MRI of the small bowel when assessing wall-thickness, lymph nodes and comb sign; good correlation was fund when assessing layered wall appearance, disease extension and fibroadipose proliferation. At MRI, time-intensity curves for 12/30 patients were active, compared with for 14/30 patients at CEUS; therefore there was a poor correlation between curve on CEUS and curve on MRI (r=0.167; p=0.36). The use of CEUS can be recommended if there is a discrepancy between MRI and clinical/laboratory parameters. MRI of the small bowel remains the most accurate method for evaluating disease activity.

Influence of exercise testing in gastroesophageal reflux in patients with gastroesophageal reflux disease.

PubMed

Mendes-Filho, Antonio Moreira; Moraes-Filho, Joaquim Prado Pinto; Nasi, Ary; Eisig, Jaime Natan; Rodrigues, Tomas Navarro; Barbutti, Ricardo Correa; Campos, Josemberg Marins; Chinzon, Decio

2014-01-01

Gastroesophageal reflux disease is a worldwide prevalent condition that exhibits a large variety of signs and symptoms of esophageal or extra-esophageal nature and can be related to the esophagic adenocarcinoma. In the last few years, greater importance has been given to the influence of physical exercises on it. Some recent investigations, though showing conflicting results, point to an exacerbation of gastroesophageal reflux during physical exercises. To evaluate the influence of physical activities in patients presenting with erosive and non erosive disease by ergometric stress testing and influence of the lower esophageal sphincter tonus and body mass index during this situation. Twenty-nine patients with erosive disease (group I) and 10 patients with non-erosive disease (group II) were prospectively evaluated. All the patients were submitted to clinical evaluation, followed by upper digestive endoscopy, manometry and 24 h esophageal pH monitoring. An ergometric testing was performed 1 h before removing the esophageal pH probe. During the ergometric stress testing, the following variables were analyzed: test efficacy, maximum oxygen uptake, acid reflux duration, gastroesophageal reflux symptoms, influence of the lower esophageal sphincter tonus and influence of body mass index in the occurrence of gastroesophageal reflux during these physical stress. Maximum oxigen consumption or VO 2 max, showed significant correlation when it was 70% or higher only in the erosive disease group, evaluating the patients with or without acid reflux during the ergometric testing (p=0,032). The other considered variables didn't show significant correlations between gastroesophageal reflux and physical activity (p>0,05). 1) Highly intensive physical activity can predispose the occurrence of gastroesophageal reflux episodes in gastroesophageal reflux disease patients with erosive disease; 2) light or short sessions of physical activity have no influence on reflux, regardless of body mass index; 3) the lower esophageal sphincter tonus does not influence the occurrence of reflux disease episodes during exercise testing.

INFLUENCE OF EXERCISE TESTING IN GASTROESOPHAGEAL REFLUX IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE

PubMed Central

MENDES-FILHO, Antonio Moreira; MORAES-FILHO, Joaquim Prado Pinto; NASI, Ary; EISIG, Jaime Natan; RODRIGUES, Tomas Navarro; BARBUTTI, Ricardo Correa; CAMPOS, Josemberg Marins; CHINZON, Décio

2014-01-01

Background Gastroesophageal reflux disease is a worldwide prevalent condition that exhibits a large variety of signs and symptoms of esophageal or extra-esophageal nature and can be related to the esophagic adenocarcinoma. In the last few years, greater importance has been given to the influence of physical exercises on it. Some recent investigations, though showing conflicting results, point to an exacerbation of gastroesophageal reflux during physical exercises. Aim To evaluate the influence of physical activities in patients presenting with erosive and non erosive disease by ergometric stress testing and influence of the lower esophageal sphincter tonus and body mass index during this situation. Methods Twenty-nine patients with erosive disease (group I) and 10 patients with non-erosive disease (group II) were prospectively evaluated. All the patients were submitted to clinical evaluation, followed by upper digestive endoscopy, manometry and 24 h esophageal pH monitoring. An ergometric testing was performed 1 h before removing the esophageal pH probe. During the ergometric stress testing, the following variables were analyzed: test efficacy, maximum oxygen uptake, acid reflux duration, gastroesophageal reflux symptoms, influence of the lower esophageal sphincter tonus and influence of body mass index in the occurrence of gastroesophageal reflux during these physical stress. Results Maximum oxigen consumption or VO 2 max, showed significant correlation when it was 70% or higher only in the erosive disease group, evaluating the patients with or without acid reflux during the ergometric testing (p=0,032). The other considered variables didn't show significant correlations between gastroesophageal reflux and physical activity (p>0,05). Conclusions 1) Highly intensive physical activity can predispose the occurrence of gastroesophageal reflux episodes in gastroesophageal reflux disease patients with erosive disease; 2) light or short sessions of physical activity have no influence on reflux, regardless of body mass index; 3) the lower esophageal sphincter tonus does not influence the occurrence of reflux disease episodes during exercise testing. PMID:24676289

Usefulness of C-Reactive Protein as a Disease Activity Marker in Crohn’s Disease according to the Location of Disease

PubMed Central

Yang, Dong-Hoon; Yang, Suk-Kyun; Park, Sang Hyoung; Lee, Ho-Su; Boo, Sun-Jin; Park, Jae-Ho; Na, Soo Young; Jung, Kee Wook; Kim, Kyung-Jo; Ye, Byong Duk; Byeon, Jeong-Sik; Myung, Seung-Jae; Kim, Jin-Ho

2015-01-01

Background/Aims C-reactive protein (CRP) is a serologic activity marker in Crohn’s disease (CD), but it may be less useful in evaluating CD activity in ileal CD patients. We aimed to investigate the usefulness of CRP as a disease activity marker in CD according to disease location. Methods Korean CD patients in a single hospital were evaluated. Factors associated with elevated CRP concentration at the time of diagnosis of CD and the association between the physician’s prediction regarding upcoming surgery and the sites of the lesions directly related to surgery were analyzed. Results Of 435 CD patients, 25.7%, 6.9%, and 67.4% had ileal, colonic, and ileocolonic CD, respectively. Multivariate analysis revealed that an elevated erythrocyte sedimentation rate, reduced serum albumin, CD activity index (CDAI) >220, and ileocolonic/colonic location were associated with an elevated CRP level and that the CRP level was significantly correlated with the CDAI in all CD patients (γ=0.466, p<0.01). However, the correlation coefficient was dependent on the location, with values of 0.395, 0.456, and 0.527 in patients with an ileal, ileocolonic, and colonic disease location, respectively. Surgery for ileal lesions was less predictable than surgery for ileocolonic or colonic lesions during follow-up. Conclusions CRP is less useful as a disease activity marker in patients with ileal CD than those with ileocolonic or colonic CD. PMID:25170056

Early response to therapy predicts 6-month and 1-year disease activity outcomes in psoriatic arthritis patients.

PubMed

Schoels, Monika M; Landesmann, Uriel; Alasti, Farideh; Baker, Daniel; Smolen, Josef S; Aletaha, Daniel

2018-06-01

In PsA management, remission and low disease activity represent preferential treatment targets. We aimed at evaluating the predictive value and clinical use of initial therapeutic response for subsequent achievement of these targets. Based on data of 216 patients enrolled in a randomized controlled trial of golimumab (GO-REVEAL), we performed diagnostic testing analyses using 3- and 6-month disease activity as tests for treatment outcomes to understand the implications of early response. In regression analyses, we estimated the probabilities for achieving at least LDA. Disease activity was measured by the disease activity index for PsA (DAPSA). Three-month DAPSA levels were excellent tests for disease activity at 6 months (and at 1 year), with areas under the receiver operating characteristic curves of 0.92 (and 0.88, respectively). The estimated probability for 6-month LDA could be quantified as <22% if patients did not reach at least moderate disease activity after 3 months on golimumab. Similar data were seen for early DAPSA response: patients achieving a DAPSA 85% at 3 months had an 84% probability for 6-month LDA or REM. All results were validated in an independent trial cohort of patients treated with infliximab (IMPACT 2). Three months after implementation of therapy in PsA, it is already possible to evaluate the potential for accomplishing therapeutic goals. This substantiates the choice of the 3-month assessment as essential for treatment adaptations.

Novel multitarget-directed ligands (MTDLs) with acetylcholinesterase (AChE) inhibitory and serotonergic subtype 4 receptor (5-HT4R) agonist activities as potential agents against Alzheimer's disease: the design of donecopride.

PubMed

Rochais, Christophe; Lecoutey, Cédric; Gaven, Florence; Giannoni, Patrizia; Hamidouche, Katia; Hedou, Damien; Dubost, Emmanuelle; Genest, David; Yahiaoui, Samir; Freret, Thomas; Bouet, Valentine; Dauphin, François; Sopkova de Oliveira Santos, Jana; Ballandonne, Céline; Corvaisier, Sophie; Malzert-Fréon, Aurélie; Legay, Remi; Boulouard, Michel; Claeysen, Sylvie; Dallemagne, Patrick

2015-04-09

In this work, we describe the synthesis and in vitro evaluation of a novel series of multitarget-directed ligands (MTDL) displaying both nanomolar dual-binding site (DBS) acetylcholinesterase inhibitory effects and partial 5-HT4R agonist activity, among which donecopride was selected for further in vivo evaluations in mice. The latter displayed procognitive and antiamnesic effects and enhanced sAPPα release, accounting for a potential symptomatic and disease-modifying therapeutic benefit in the treatment of Alzheimer's disease.

Serum Adipocytokine Levels as Surrogate Markers for Disease Activity of Crohn's Disease.

PubMed

Kim, Su Hwan; Jang, Seung Hyeon; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae; Kim, You Sun; Han, Dong Soo; Kim, Joo Sung

2017-05-01

Determining inflammatory activity is crucial for assessing disease activity and for tailoring therapy in patients with Crohn׳s disease (CD). This study aimed to evaluate adipocytokine levels in patients with CD and to determine whether they can serve as surrogate markers for disease activity. Serum samples and information regarding the clinical features of patients in the CD Network Project registry were collected from March 2009 to February 2012. Patients with CD and disease duration of at least 2 years were enrolled in this study. Fasting serum leptin, adiponectin, obestatin and ghrelin levels were measured, and their correlation with clinical features of the patients was analyzed. Serum adipocytokine levels were evaluated according to disease activity as determined by CD activity index score. A total of 153 patients with CD were included. Serum ghrelin levels negatively correlated with patient age (P = 0.041) and age at diagnosis (P = 0.017), and positively correlated with C-reactive protein (CRP) levels (P = 0.017). Multiple regression analysis showed that serum ghrelin levels were related only to CRP levels (P = 0.032). Like ghrelin, serum leptin levels were also related to CRP levels (P < 0.001). Obestatin and adiponectin levels were not related to CRP levels. Serum adipocytokine levels did not significantly differ across different disease locations or behaviors. Serum ghrelin levels were significantly lower in patients with CD with a history of surgery than in those without (P = 0.007). Serum ghrelin and leptin levels may be useful as surrogate markers for disease activity in patients with CD. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Inflammatory activity in Crohn disease: ultrasound findings.

PubMed

Migaleddu, Vincenzo; Quaia, Emilio; Scano, Domenico; Virgilio, Giuseppe

2008-01-01

Improvements in the ultrasound examination of bowel disease have registered in the last years the introduction of new technologies regarding high frequency probes (US), highly sensitive color or power Doppler units (CD-US), and the development of new non-linear technologies that optimize detection of contrast agents. Contrast-enhanced ultrasound (CE-US) most importantly increases the results in sonographic evaluation of Crohn disease inflammatory activity. CE-US has become an imaging modality routinely employed in the clinical practice for the evaluation of parenchymal organs due to the introduction of new generation microbubble contrast agents which persist in the bloodstream for several minutes after intravenous injection. The availability of high frequency dedicated contrast-specific US techniques provide accurate depiction of small bowel wall perfusion due to the extremely high sensitivity of non-linear signals produced by microbubble insonation. In Crohn's disease, CE-US may characterize the bowel wall thickness by differentiating fibrosis from edema and may grade the inflammatory disease activity by assessing the presence and distribution of vascularity within the layers of the bowel wall (submucosa alone or the entire bowel wall). Peri-intestinal inflammatory involvement can be also characterized. CE-US can provide prognostic data concerning clinical recurrence of the inflammatory disease and evaluate the efficacy of drugs treatments.

Inflammatory bowel disease imaging: Current practice and future directions

PubMed Central

Kilcoyne, Aoife; Kaplan, Jess L; Gee, Michael S

2016-01-01

The purpose of this paper is to evaluate the role of imaging in inflammatory bowel disease (IBD), including detection of extraluminal complications and extraintestinal manifestations of IBD, assessment of disease activity and treatment response, and discrimination of inflammatory from fibrotic strictures. IBD is a chronic idiopathic disease affecting the gastrointestinal tract that is comprised of two separate, but related intestinal disorders; Crohn’s disease and ulcerative colitis. The paper discusses, in detail the pros and cons of the different IBD imaging modalities that need to be considered in order to optimize the imaging and clinical evaluation of patients with IBD. Historically, IBD evaluation of the bowel has included imaging to assess the portions of the small bowel that are inaccessible to optical endoscopic visualization. This traditionally was performed using barium fluoroscopic techniques; however, cross-sectional imaging techniques (computed tomography and magnetic resonance imaging) are being increasingly utilized for IBD evaluation because they can simultaneously assess mural and extramural IBD manifestations. Recent advances in imaging technology, that continue to improve the ability of imaging to noninvasively follow disease activity and treatment response, are also discussed. This review article summarizes the current imaging approach in inflammatory bowel disease as well as the role of emerging imaging modalities. PMID:26811637

Sarcopenia in rheumatoid arthritis: prevalence, influence of disease activity and associated factors.

PubMed

Ngeuleu, Ange; Allali, F; Medrare, L; Madhi, A; Rkain, H; Hajjaj-Hassouni, N

2017-06-01

Evaluate the prevalence of sarcopenia on patients with rheumatoid arthritis (RA), the influence of sarcopenia on disease activity and factors associated with sarcopenia. One hundred and twenty-three patients aged over 18 years with RA based on the 1987 ACR/EULAR classification criteria were enrolled. We performed a whole body DXA scan using a dual-energy X-ray absorptiometry (DXA) scanner lunar prodigy to measure fat mass, lean mass, and bone mass in the whole body and body parts. According to the anthropometric equation by Baumgartner et al., sarcopenia was defined as Relative skeletal mass index (RSMI) <5.5 kg/m 2 on women and <7.26 kg/m 2 on men. Body mass index (BMI) and waist circumference were measured and patients were classified according to World Health Organization. Disease activity was evaluated by: disease activity score 28 ESR (DAS28 ESR), disease activity score 28 CRP (DAS28 CRP), clinical disease activity index (CDAI), simplify disease activity index (SDAI). We measured functional disability by Health assessment questionnaire (HAQ). History and previous medication use including steroids were also checked, and comorbidities were recorded. We analyzed the relation between disease parameters and sarcopenia with the r of Pearson and Spearman. Factors associated and related to sarcopenia were assessed using multiple regression analysis and t independent test. We included 123 patients (107 women). 49 subjects (39.8%) where suffering from sarcopenia, of which 40 women. Most of the sarcopenic patients were between 41 and 50 years old. Sarcopenia on female subjects was not related to parameters of disease activity evaluated by DAS 28, CDAI and SDAI. Most of the sarcopenic patients had normal BMI and abnormal waist circumference. In simple regression analysis sarcopenia was related to BMI, DAS 28 ESR, bone erosion, waist circumference and HAQ. In multiple regression analysis, sarcopenia was positively related to an increase cardiometabolic risk [p = 0.025, OR 0.176, CI (0.038-0.980)], normal BMI [p = 0.004, OR 12.3, CI (2.27-67.6)], over fat BMI [p = 0.004, OR 12.3, CI (2.27-67.6)] and bone erosion [p = 0.012, OR 0.057 CI (0.006-0.532)]. No statistical difference was found according to disease duration and steroids use between sarcopenic and non sarcopenic patients. Sarcopenia is prevalent and related to age, bone erosion, normal/over fat BMI and high cardiometabolic risk according to waist circumference but not with disease activity.

Evidences of Herbal Medicine-Derived Natural Products Effects in Inflammatory Lung Diseases.

PubMed

Santana, Fernanda Paula R; Pinheiro, Nathalia M; Mernak, Márcia Isabel B; Righetti, Renato F; Martins, Mílton A; Lago, João H G; Lopes, Fernanda D T Q Dos Santos; Tibério, Iolanda F L C; Prado, Carla M

2016-01-01

Pulmonary inflammation is a hallmark of many respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory syndrome distress (ARDS). Most of these diseases are treated with anti-inflammatory therapy in order to prevent or to reduce the pulmonary inflammation. Herbal medicine-derived natural products have been used in folk medicine and scientific studies to evaluate the value of these compounds have grown in recent years. Many substances derived from plants have the biological effects in vitro and in vivo, such as flavonoids, alkaloids, and terpenoids. Among the biological activities of natural products derived from plants can be pointed out the anti-inflammatory, antiviral, antiplatelet, antitumor anti-allergic activities, and antioxidant. Although many reports have evaluated the effects of these compounds in experimental models, studies evaluating clinical trials are scarce in the literature. This review aims to emphasize the effects of these different natural products in pulmonary diseases in experimental models and in humans and pointing out some possible mechanisms of action.

Cerebral Embolic Activity in a Patient during Acute Crisis of Takayasu's Arteritis

PubMed Central

Nogueira, Ricardo de Carvalho; Bor-Seng-Shu, Edson; Marchiori, Paulo Eurípedes; Teixeira, Manoel Jacobsen

2012-01-01

Takayasu's arteritis is a disease that affects large vessels and may cause neurological symptoms either by stenoses/occlusions or embolisms from vessels with an inflammatory process. Transcranial Doppler (TCD) ultrasound can provide useful information for diagnosis and monitoring during the active phase of the disease. Cerebral embolic signals can be detected by TCD and have been considered a risk factor for vascular events. We report a patient in whom TCD ultrasound was used to monitor cerebral embolic signals during the active phase of the disease. This case report suggests that embolic activity in Takayasu's arteritis may represent disease activity, and its monitoring may be useful for evaluating the response to therapy. PMID:22379479

Spinsterhood and its impact on disease features in women with rheumatoid arthritis.

PubMed

Yacoub, Yousra Ibn; Amine, Bouchra; Laatiris, Assia; Hajjaj-Hassouni, Najia

2011-08-01

To evaluate the impact of spinsterhood on disease characteristics and quality of life (QoL) in Moroccan women with rheumatoid arthritis (RA). 185 women with RA were recruited in this study. Marital status was specified as follow: 1. Spinsterhood (never-married woman aged 38 or over), 2. Distressed marriage; 3. Nondistressed marriage and 4. Divorced or widowed. Marital distress was assessed by a self-report concerning coping efficacy and burden caring of husbands. Assessment criteria included the evaluation of: age at onset (years), diagnosis delay (months), disease duration (years), disease activity (evaluated by physical examination, biological inflammatory tests; and disease activity score (DAS 28)), pain intensity (measured with a visual analogue scale (VAS)); and radiographic damage (evaluated by the Sharp's method as modified by van der Heijde). Treatments (doses and duration) were specified. The Health Assessment Questionnaire (HAQ) was used to evaluate functional disability. QoL was measured using the Arabic version of the generic instrument SF-36. In our data, spinsterhood was detected in 42 (22.7%) patients vs. 88 (47.5%) with distressed marriage, 28 (15.1%) with nondistressed marriage and 27 (14.6%) divorced or widowed. Comparing the 4 groups, we found that QoL in never-married women was damaged in a significant way comparing to the other groups. Mental as well as physical aspects were affected. Also, we found that spinsterhood was associated to an early age at onset (p = 0.009), pain intensity (p < 0.001); clinical (p < 0.001) and biological disease activity (C-reactive protein; p = 0.02) and functional disability (p < 0.001). Logistic regression analysis revealed a significant relationship between spinsterhood and early age at onset and severe functional disability (for all p ≤ 0.01). This study suggests that spinsterhood in our RA patients was associated with an altered QoL even compared with distressed married women. Also, we state that spinsterhood was associated with an early age at onset, severe joint pain; higher disease activity and with altered functional ability. It seems important to consider not only disease-related parameters but also social status as a determinant factor of poor course in RA.

Effect of Xerostomia on the Functional Capacity of Subjects with Rheumatoid Arthritis.

PubMed

Lins E Silva, Marília; Carvalho, Camila Nunes; Carvalho, Alessandra de Albuquerque Tavares; Leão, Jair Carneiro; Duarte, Angela Luzia Pinto; Gueiros, Luiz Alcino

2016-10-01

To evaluate the intensity of xerostomia and hyposalivation in subjects with rheumatoid arthritis (RA) as well as the effects of these conditions on functional incapacity and disease activity. The study sample comprised 236 individuals of both sexes who had RA. All the individuals were submitted to clinical evaluation and unstimulated sialometry. Functional capacity was determined by using the Health Assessment Questionnaire (HAQ), xerostomia was assessed using the Xerostomia Inventory, and disease activity was evaluated with the 28-joint Disease Activity Score (DAS28). The effect of Sjögren syndrome (SS) was analyzed, and the sample was divided into 2 groups: RA (191 subjects) and RA/SS (45 subjects). The Xerostomia Inventory showed positive and significant correlation with fatigue (r = 0.243; p < 0.0001), number of painful joints (r = 0.218; p = 0.001), HAQ (r = 0.279; p < 0.0001), and DAS28 (r = 0.156; p < 0.0001). On regression analysis, both xerostomia (OR 3.89, 95% CI 1.84-8.23, p < 0.001) and DAS28 (for severe disease activity: OR 13.26, 95% CI 3.15-55.79, p < 0.001) showed influence on functional incapacity. Forty-five individuals (19.1%) presented with secondary SS, and having this diagnosis was not associated with disease activity or functional capacity. Xerostomia demonstrated an adverse effect on quality of life of subjects with RA, being associated with a reduction in functional capacity. In this clinical setting, xerostomia can be monitored as a marker of worse clinical evolution.

Sexual Dysfunctions in Men and Women with Inflammatory Bowel Disease: The Influence of IBD-Related Clinical Factors and Depression on Sexual Function.

PubMed

Bel, Linda G J; Vollebregt, Anna M; Van der Meulen-de Jong, Andrea E; Fidder, Herma H; Ten Hove, Willem R; Vliet-Vlieland, Cornelia W; Ter Kuile, Moniek M; de Groot, Helena E; Both, Stephanie

2015-07-01

Inflammatory bowel disease (IBD) is likely to have an impact on sexual function because of its symptoms, like diarrhea, fatigue, and abdominal pain. Depression is commonly reported in IBD and is also related to impaired sexual function. This study aimed to evaluate sexual function and its association with depression among patients with IBD compared with controls. IBD patients registered at two hospitals participated. The control group consisted of a general practitioner practice population. The web-based questionnaire included the Female Sexual Function Index (FSFI) for women and the International Index of Erectile Function (IIEF) for men. Other variables evaluated were depression, disease activity, IBD-related quality of life, body image, and fatigue. In total, 168 female and 119 male patients were available for analysis (response rate 24%). Overall, patients with IBD did not significantly differ in prevalence of sexual dysfunctions from controls: female patients 52%, female controls 44%, male patients and male controls both 25%. However, men and women with an active disease scored significantly lower than patients in remission and controls, indicating impaired sexual functioning during disease activity. Significant associations were found between active disease, fatigue, depressive mood, quality of life, and sexual function for both male and female patients. The association between disease activity and sexual function was totally mediated by depression. Male and female IBD patients with an active disease show impaired sexual function relative to patients in remission and controls. Depression is the most important determinant for impaired sexual function in IBD. © 2015 International Society for Sexual Medicine.

Disease activity in chronic inflammatory demyelinating polyneuropathy.

PubMed

Albulaihe, Hana; Alabdali, Majed; Alsulaiman, Abdulla; Abraham, Alon; Breiner, Ari; Barnett, Carolina; Katzberg, Hans D; Lovblom, Leif E; Perkins, Bruce A; Bril, Vera

2016-10-15

Evaluation of disease status in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is often done by a combination of clinical evaluation and electrodiagnostic studies. A CIDP disease activity status (CDAS) was developed to standardize outcomes in CIDP patients. We aimed to determine if the CDAS was concordant with classical evaluation and whether CDAS enables benchmarking of CIDP. We performed a retrospective chart review of 305 CIDP patients and identified 206 patients with >1 visit and applied the CDAS to this cohort. We examined relationships between the CDAS and classical evaluation as to outcomes and compared our cohort to other CIDP cohorts who had CDAS. We found that the CDAS mirrored disease severity as measured by electrophysiology and vibration perception thresholds in that CDAS class 5 had more severe neuropathy. Our results are similar to other cohorts in the middle CDAS strata with the exception of fewer subjects in CDAS 1 and more in CDAS 5. The only demographic factor predicting CDAS 5 in our cohort was age, and the overall treatment response rate using the CDAS classification was 79.3%. CDAS appears to have sufficient face-validity as a grading system to assess disease activity in relation to treatment status. The use of CDAS appears to allow benchmarking of patients with CIDP that may be useful in subject selection for clinical trials and also to highlight differences in practice. Copyright © 2016 Elsevier B.V. All rights reserved.

Endoscopic Scores for Evaluation of Crohn's Disease Activity at Small Bowel Capsule Endoscopy: General Principles and Current Applications.

PubMed

Rosa, Bruno; Pinho, Rolando; de Ferro, Susana Mão; Almeida, Nuno; Cotter, José; Saraiva, Miguel Mascarenhas

2016-01-01

The small bowel is affected in the vast majority of patients with Crohn's Disease (CD). Small bowel capsule endoscopy (SBCE) has a very high sensitivity for the detection of CD-related pathology, including early mucosal lesions and/or those located in the proximal segments of the small bowel, which is a major advantage when compared with other small bowel imaging modalities. The recent guidelines of European Society of Gastrointestinal Endoscopy (ESGE) and European Crohn's and Colitis Organisation (ECCO) advocate the use of validated endoscopic scoring indices for the classification of inflammatory activity in patients with CD undergoing SBCE, such as the Lewis Score or the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI). These scores aim to standardize the description of lesions and capsule endoscopy reports, contributing to increase inter-observer agreement and enabling a stratification of the severity of the disease. On behalf of the Grupo de Estudos Português do Intestino Delgado (GEPID) - Portuguese Small Bowel Study Group, we aimed to summarize the general principles and clinical applications of current endoscopic scoring systems for SBCE in the setting of CD, covering the topic of suspected CD as well as the evaluation of disease extent (with potential prognostic and therapeutic impact), evaluation of mucosal healing in response to treatment and evaluation of post-surgical recurrence in patients with previously established diagnosis of CD.

A Survey on the Willingness to Use Physical Activity Smartphone Applications (Apps) in Patients with Chronic Diseases.

PubMed

Sun, Liu; Jiao, Chen; Wang, Yanling; Xiao, Qian; Zhang, Yiling; Wu, Ying

2016-01-01

This study aimed to explore the willingness of using physical activity smartphone apps among patients with chronic diseases. 218 outpatients from a tertiary hospital in Beijing were involved using a questionnaire. Over half of the patients (53.7%) were willing to use smartphone apps to promote physical activities. The individuals more likely to use physical activity apps tended to be younger (≤44 years), be more educated, perceiving their disease need exercise instruction or professional support, current smartphone user, having previous experience of using physical activity apps, and accepting paid apps (P<0.05). The results could help health educator suggest chronic disease patients to use apps to do more exercises. Further research could be focus on evaluate the effects of using physical activity apps in chronic disease patients.

Reduction of nitric oxide and DNA/RNA oxidation products are associated with active disease in systemic lupus erythematosus patients.

PubMed

Iriyoda, T M V; Stadtlober, N; Lozovoy, M A B; Delongui, F; Costa, N T; Reiche, E M V; Dichi, I; Simão, A N C

2017-09-01

The aims of the present study were to evaluate biomarkers of oxidative and nitrosative stress in systemic lupus erythematosus (SLE) patients, in particular products of DNA/RNA oxidative damage and their correlation with disease activity. This study included 188 controls and 203 patients; 153 with inactive SLE (SLEDAI < 6) and 50 with active SLE (SLEDAI ≥ 6) without renal impairment. Oxidative stress was assessed by tert-butyl hydroperoxide-initiated by chemiluminescence, advanced oxidation protein products (AOPP), total radical-trapping antioxidant parameter (TRAP), nitric oxide metabolites (NOx), and DNA/RNA oxidation products. Patients with SLE showed increased oxidative stress, as demonstrated by the augmentation of lipid hydroperoxides ( p < 0.0001) and AOPP ( p < 0.001) and reduced total antioxidant capacity ( p < 0.0001), without differences between patients with active disease and in remission. NOx levels and DNA/RNA oxidation products were inversely and independently associated with disease activity ( p < 0.0001 and p = 0.021, respectively), regardless of BMI and prednisone use. The linear regression analysis showed that about 5% of the SLEDAI score can be explained by the levels of DNA/RNA oxidation products ( r 2 :0.051; p = 0.002) and about 9% of this score by the levels of NOx ( r 2 :0.091; p < 0.0001). This study provides evidence for an inverse association between serum NOx levels and DNA/RNA oxidation products and SLE disease activity, suggesting that oxidative/nitrosative stress markers may be useful in evaluating SLE disease activity and progression of the disease.

Quality of Life in Swiss Paediatric Inflammatory Bowel Disease Patients: Do Patients and Their Parents Experience Disease in the Same Way?

PubMed Central

Mueller, Rebekka; Ziade, Farah; Pittet, Valérie; Fournier, Nicolas; Ezri, Jessica; Schoepfer, Alain; Schibli, Susanne; Spalinger, Johannes; Braegger, Christian

2016-01-01

Background and Aims: Inflammatory bowel diseases (IBDs) may impair quality of life (QoL) in paediatric patients. We aimed to evaluate in a nationwide cohort whether patients experience QoL in a different way when compared with their parents. Methods: Sociodemographic and psychosocial characteristics were prospectively acquired from paediatric patients and their parents included in the Swiss IBD Cohort Study. Disease activity was evaluated by the Paediatric Crohn’s Disease Activity Index (PCDAI) and the Paediatric Ulcerative Colitis Activity Index (PUCAI). We assessed QoL using the KIDSCREEN questionnaire. The QoL domains were analysed and compared between children and parents according to type of disease, parents’ age, origin, education and marital status. Results: We included 110 children and parents (59 Crohn’s disease [CD], 45 ulcerative colitis [UC], 6 IBD unclassified [IBDU]). There was no significant difference in QoL between CD and UC/IBDU, whether the disease was active or in remission. Parents perceived overall QoL, as well as ‘mood’, ‘family’ and ‘friends’ domains, lower than the children themselves, independently of their place of birth and education. However, better concordance was found on ‘school performance’ and ‘physical activity’ domains. Marital status and age of parents significantly influenced the evaluation of QoL. Mothers and fathers being married or cohabiting perceived significantly lower mood, family and friends domains than their children, whereas mothers living alone had a lower perception of the friends domain; fathers living alone had a lower perception of family and mood subscores. Conclusion: Parents of Swiss paediatric IBD patients significantly underestimate overall QoL and domains of QoL of their children independently of origin and education. PMID:26519462

Impact of Physical Activity in Cardiovascular and Musculoskeletal Health: Can Motion Be Medicine?

PubMed Central

Curtis, Gannon L.; Chughtai, Morad; Khlopas, Anton; Newman, Jared M.; Khan, Rafay; Shaffiy, Shervin; Nadhim, Ali; Bhave, Anil; Mont, Michael A.

2017-01-01

Physical activity is a well-known therapeutic tool for various types of medical conditions, including vasculopathic diseases such as coronary artery disease, stroke, type 2 diabetes, and obesity. Additionally, increased physical activity has been proposed as a therapy to improve musculoskeletal health; however, there are conflicting reports about physical activity potentially leading to degenerative musculoskeletal disease, especially osteoarthritis (OA). Additionally, although physical activity is known to have its benefits, it is unclear as to what amount of physical activity is the most advantageous. Too much, as well as not enough exercise can have negative consequences. This could impact how physicians advise their patients about exercise intensity. Multiple studies have evaluated the effect of physical activity on various aspects of health. However, there is a paucity of systematic studies which review cardiovascular and musculoskeletal health as outcomes. Therefore, the purpose of this review was to assess how physical activity impacts these aspects of health. Specifically, we evaluated the effect of various levels of physical activity on: 1) cardiovascular and 2) musculoskeletal health. The review revealed that physical activity may decrease cardiovascular disease and improve OA symptoms, and therefore, motion can be considered a “medicine”. However, because heavy activity can potentially lead to increased OA risk, physicians should advise their patients that excessive activity can also potentially impact their health negatively, and should be done in moderation, until further study. PMID:28392856

INCREASED TISSUE TRANSGLUTAMINASE LEVELS ARE ASSOCIATED WITH INCREASED EPILEPTIFORM ACTIVITY IN ELECTROENCEPHALOGRAPHY AMONG PATIENTS WITH CELIAC DISEASE.

PubMed

Işikay, Sedat; Hizli, Şamil; Çoşkun, Serkan; Yilmaz, Kutluhan

2015-12-01

Celiac disease is an autoimmune systemic disorder in genetically predisposed individuals precipitated by gluten ingestion. In this study, we aimed to determine asymptomatic spike-and-wave findings on electroencephalography in children with celiac disease. A total of 175 children with the diagnosis of celiac disease (study group) and 99 age- and sex-matched healthy children as controls (control group) were included in the study. In order to determine the effects of gluten free diet on laboratory and electroencephalography findings, the celiac group is further subdivided into two as newly-diagnosed and formerly-diagnosed patients. Medical histories of all children and laboratory findings were all recorded and neurologic statuses were evaluated. All patients underwent a sleep and awake electroencephalography. Among 175 celiac disease patients included in the study, 43 were newly diagnosed while 132 were formerly-diagnosed patients. In electroencephalography evaluation of patients the epileptiform activity was determined in 4 (9.3%) of newly diagnosed and in 2 (1.5%) of formerly diagnosed patients; on the other hand the epileptiform activity was present in only 1 (1.0%) of control cases. There was a statistically significant difference between groups in regards to the presence of epileptiform activity in electroencephalography. Pearson correlation analysis revealed that epileptiform activity in both sleep and awake electroencephalography were positively correlated with tissue transglutaminase levels (P=0.014 and P=0.019, respectively). We have determined an increased epileptiform activity frequency among newly-diagnosed celiac disease patients compared with formerly-diagnosed celiac disease patients and control cases. Moreover the tissue transglutaminase levels were also correlated with the presence of epileptiform activity in electroencephalography. Among newly diagnosed celiac disease patients, clinicians should be aware of this association and be alert about any neurological symptoms.

The Localized Scleroderma Cutaneous Assessment Tool: responsiveness to change in a pediatric clinical population.

PubMed

Kelsey, Christina E; Torok, Kathryn S

2013-08-01

Lack of agreement on how to accurately capture disease outcomes in localized scleroderma (LS) has hindered the development of efficacious treatment protocols. The LS Cutaneous Assessment Tool (LoSCAT), consisting of the modified LS Skin Severity Index (mLoSSI) and the LS Damage Index, has potential for use in clinical trials. The goal of this article is to further evaluate the clinical responsiveness of the LoSCAT. Based on the modifiable nature of disease activity versus damage, we expected the mLoSSI to be responsive to change. At 2 study visits, a physician completed the LoSCAT and Physician Global Assessment (PGA) of Disease Activity and of Disease Damage for 29 patients with LS. Spearman correlations were used to examine the relationships between the change in the LoSCAT and the PGA scores. To evaluate contrasted group validity, patients were grouped according to disease activity classification and change scores of groups were compared. Minimal clinically important differences were calculated and compared with the standard error of measurement. Change in the mLoSSI score correlated strongly with change in the PGA of Disease Activity score, whereas change in the LS Damage Index score correlated weakly with change in the PGA of Disease Damage score. The mLoSSI and PGA of Disease Activity exhibited contrasted group validity. Minimal clinically important differences for the activity measures were greater than the respective standard errors of measurement. Only 2 study visits were included in analysis. This study gives further evidence that the LoSCAT, specifically the mLoSSI, is a responsive, valid measure of activity in LS and should be used in future treatment studies. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Evaluation of spondylarthritis activity by patients and physicians: ASDAS, BASDAI, PASS, and flares in 200 patients.

PubMed

Godfrin-Valnet, Marie; Prati, Clément; Puyraveau, Marc; Toussirot, Eric; Letho-Gyselink, Hélène; Wendling, Daniel

2013-07-01

In patients with spondyloarthritis, to determine Ankylosing Spondylitis Disease Activity Score (ASDAS) cutoffs matching the patient-acceptable symptom state (PASS) and patient-reported levels of disease activity, to assess associations between disease activity levels and presence of depression, and to identify ASDAS and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) cutoffs indicating a flare and indicating a remission. Prospective single-center study of patients meeting ASAS criteria for spondyloarthritis receiving follow-up at the Besançon teaching hospital, France, between February 2011 and February 2012. In each patient, the BASDAI, ASDAS, Bath Ankylosing Spondylitis Functional Index (BASFI), patient-acceptable symptom state (PASS) and signs of depression were assessed. Receiver-operating characteristic (ROC) curves were drawn to identify the ASDAS cutoffs separating different levels of disease activity. The kappa coefficient was computed to evaluate agreement between patients and physicians regarding the presence of flares. Two hundred patients with a mean age of 44.4 ± 12.5 years and mean disease duration of 12.9 ± 10.5 years were included. Mean BASDAI was 4.1 ± 2.2, mean ASDAS-C-reactive protein (CRP) was 2.4 ± 1, mean BASFI was 3.3 ± 2.7, and 58.9% of patients reported being in the PASS. The PASS was associated with BASDAI values inferior or equal to 4.1 and ASDAS-CRP values inferior or equal to 2.3. Mild patient-reported disease activity was associated with BASDAI values inferior or equal to 3.8 and ASDAS-CRP values inferior or equal to 2.3; corresponding values for high patient-reported disease activity were superior to 5.2 and superior to 3.1. Among patients reporting high disease activity, 64.5% had Beck Depression Inventory scores consistent with severe depression. At the time of the visit, 36.9% of the patients and 28.3% of the physicians felt there was a flare. Cutoffs indicating a flare were superior or equal to 5.2 for the BASDAI and superior or equal to 2.3 for the ASDAS-CRP. Agreement between patients and physicians regarding flares was good (Kappa, 0.61). An evaluation in 43 patients indicated that an ASDAS-CRP cutoff inferior or equal to 2.2 separated the 25.6% of patients who reported being in remission from the other patients. Our results show a significant association between disease activity and depression severity, as well as good agreement between BASDAI and ASDAS. The ASDAS cutoffs for the various levels of patient-reported disease activity differed from the cutoffs suggested by ASAS; a 2.3 cutoff was found for both patient-reported absence of disease activity and PASS, indicating that achieving PASS should be included among our treatment objectives. Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Analysis of fat and muscle mass in patients with inflammatory bowel disease during remission and active phase.

PubMed

Rocha, Raquel; Santana, Genoile Oliveira; Almeida, Neogélia; Lyra, Andre Castro

2009-03-01

Inflammatory bowel disease (IBD) is often associated with malnutrition. The aim of this study was to compare the body composition of outpatients with IBD during remission and active phase. In order to evaluate disease activity we used Crohn's Disease Activity Index for Crohn's disease (CD) patients and Lichtiger's Index for ulcerative colitis (UC) patients. All patients underwent the analysis of BMI, arm muscle area (AMA) and triceps plus subscapula skinfold thickness (TST+SST) to identify total, muscle and fat mass, respectively. In total 102 patients were evaluated (CD, n 50; UC, n 52) and the majority was young women. Malnutrition according to BMI was found in 14.0 % of patients with CD and 5.7 % of UC patients. Muscle mass depletion was detected in more than half of the CD and UC patients. The BMI, TST+SST and AMA values were lower in the active phase only in CD patients (P < 0.05). Fat mass depletion was associated with active phase in both CD and UC patients. Body composition parameters obtained using BMI, TST+SST and AMA were not correlated with the presence of fistula in CD patients (P>0.05). In conclusion, patients without signs of malnutrition had fat mass depletion especially in the active phase and muscle mass depletion occurred both in CD and UC patients.

78 FR 20319 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-04

... GH13-004; Monitoring and Evaluation of Malaria Control and Elimination Activities, FOA GH13-005; and...; Monitoring and Evaluation of Malaria Control and Elimination Activities, FOA GH13-005; and Research and...

Effect of rivastigmine on plasma butyrylcholine esterase activity and plasma ghrelin levels in patients with dementia in Alzheimer's disease.

PubMed

Kuroda, Atsushi; Setoguchi, Manabu; Uchino, Yasushi; Nagata, Kazuya; Hokonohara, Daisuke

2018-02-14

Alzheimer's disease causes loss of appetite, resulting in bodyweight reduction. This, in turn, causes progression of cognitive dysfunction and physical complications that hasten death. Earlier care for loss of appetite is essential in Alzheimer's disease management. Rivastigmine is a therapeutic agent for Alzheimer's disease that has dual inhibition effects on acetylcholine esterase and butyrylcholine esterase. Butyrylcholine esterase is known to degrade the gastric hormone, ghrelin, which regulates appetite; therefore, we considered that rivastigmine might have an effect on appetite. The present study aimed to evaluate the hypothesis that rivastigmine improves appetite in Alzheimer's disease patients. Rivastigmine was given to mild-to-moderate Alzheimer's disease patients for 16 weeks. We evaluated the effects of rivastigmine on food intake, bodyweight, motivation (estimated by the vitality index), cognition function (estimated by the Hasegawa Dementia Scale-Revised), plasma butyrylcholine esterase activity, active ghrelin and inactive ghrelin. Plasma butyrylcholine esterase activity significantly decreased over time (percent change: -18.9 ± 27.0%, P < 0.05 at week 8; percent change: -33.4 ± 45.4%, P < 0.05 at week 16). Negative correlations were detected between percent changes in butyrylcholine esterase activity and active ghrelin (r s  = -0.62, P = 0.033) or active/inactive ghrelin ratio (r s  = -0.73, P = 0.007). Furthermore, motivation (including appetite) improved significantly (percent change: 17.9 ± 18.6%, P < 0.05 at week 16). The present study suggests that rivastigmine might improve appetite in mild-to-moderate Alzheimer's disease patients by suppressing degradation of plasma active ghrelin through the inhibition of plasma butyrylcholine esterase. Geriatr Gerontol Int 2018; ••: ••-••. © 2018 Japan Geriatrics Society.

Long-Term Performance of Readers Trained in Grading Crohn Disease Activity Using MRI.

PubMed

Puylaert, Carl A J; Tielbeek, Jeroen A W; Bipat, Shandra; Boellaard, Thierry N; Nio, C Yung; Stoker, Jaap

2016-12-01

We aim to evaluate the long-term performance of readers who had participated in previous magnetic resonance imaging (MRI) reader training in grading Crohn disease activity. Fourteen readers (8 women; 12 radiologists, 2 residents; mean age 40; range 31-59), who had participated in a previous MRI reader training, participated in a follow-up evaluation after a mean interval of 29 months (range 25-34 months). Follow-up evaluation comprised 25 MRI cases of suspected or known Crohn disease patients with direct feedback; cases were identical to the evaluation set used in the initial reader training (of which readers were unaware). Grading accuracy, overstaging, and understaging were compared between training and follow-up using a consensus score by two experienced abdominal radiologists as the reference standard. In the follow-up evaluation, overall grading accuracy was 73% (95% confidence interval [CI]: 62%-81%), which was comparable to reader training grading accuracy (72%, 95% CI: 61%-80%) (P = .66). Overstaging decreased significantly from 19% (95% CI: 12%-27%) to 13% (95% CI: 8%-21%) between training and follow-up (P = .03), whereas understaging increased significantly from 9% (95% CI: 4%-21%) to 14% (95% CI: 7%-26%) (P < .01). Readers have consistent long-term accuracy for grading Crohn disease activity after case-based reader training with direct feedback. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

In Celiac Disease, a Subset of Autoantibodies against Transglutaminase Binds Toll-Like Receptor 4 and Induces Activation of Monocytes

PubMed Central

Tridente, Giuseppe; Bason, Caterina; Sivori, Simona; Beri, Ruggero; Dolcino, Marzia; Valletta, Enrico; Corrocher, Roberto; Puccetti, Antonio

2006-01-01

Background Celiac disease is a small intestine inflammatory disorder with multiple organ involvement, sustained by an inappropriate immune response to dietary gluten. Anti-transglutaminase antibodies are a typical serological marker in patients with active disease, and may disappear during a gluten-free diet treatment. Involvement of infectious agents and innate immunity has been suggested but never proven. Molecular mimicry is one of the mechanisms that links infection and autoimmunity. Methods and Findings In our attempt to clarify the pathogenesis of celiac disease, we screened a random peptide library with pooled sera of patients affected by active disease after a pre-screening with the sera of the same patients on a gluten-free diet. We identified a peptide recognized by serum immunoglobulins of patients with active disease, but not by those of patients on a gluten-free diet. This peptide shares homology with the rotavirus major neutralizing protein VP-7 and with the self-antigens tissue transglutaminase, human heat shock protein 60, desmoglein 1, and Toll-like receptor 4. We show that antibodies against the peptide affinity-purified from the sera of patients with active disease recognize the viral product and self-antigens in ELISA and Western blot. These antibodies were able to induce increased epithelial cell permeability evaluated by transepithelial flux of [3H] mannitol in the T84 human intestinal epithelial cell line. Finally, the purified antibodies induced monocyte activation upon binding Toll-like receptor 4, evaluated both by surface expression of activation markers and by production of pro-inflammatory cytokines. Conclusions Our findings show that in active celiac disease, a subset of anti-transglutaminase IgA antibodies recognize the viral protein VP-7, suggesting a possible involvement of rotavirus infection in the pathogenesis of the disease, through a mechanism of molecular mimicry. Moreover, such antibodies recognize self-antigens and are functionally active, able to increase intestinal permeability and induce monocyte activation. We therefore provide evidence for the involvement of innate immunity in the pathogenesis of celiac disease through a previously unknown mechanism of engagement of Toll-like receptor 4. PMID:16984219

The clinical relevance of plasma CD147/basigin in biopsy-proven kidney diseases.

PubMed

Mori, Yoshiko; Masuda, Tomohiro; Kosugi, Tomoki; Yoshioka, Tomoki; Hori, Mayuko; Nagaya, Hiroshi; Maeda, Kayaho; Sato, Yuka; Kojima, Hiroshi; Kato, Noritoshi; Ishimoto, Takuji; Katsuno, Takayuki; Yuzawa, Yukio; Kadomatsu, Kenji; Maruyama, Shoichi

2017-12-12

Precise understanding of kidney disease activity is needed to design therapeutic strategies. CD147/basigin is involved in the pathogenesis of acute kidney injury and renal fibrosis through inflammatory cell infiltration. The present study examined the clinical relevance of CD147 in biopsy-proven kidney diseases that lead to the progression of chronic kidney disease. Kidney biopsy specimens and plasma and urine samples were obtained from patients with kidney diseases, including IgA nephropathy (IgAN), Henoch-Schönlein purpura nephritis (HSPN), diabetic kidney disease (DKD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN), who underwent renal biopsy between 2011 and 2014. Plasma and urinary CD147 levels were measured and evaluated for their ability to reflect histological features. Disease activity of IgAN tissues was evaluated according to the Oxford classification and the Japanese histological grading system. In biopsy tissues, CD147 induction was detected in injured lesions representing renal inflammation. Plasma CD147 values correlated with eGFR in patients with inflammation-related kidney diseases such as IgAN, HSPN, and DKD. Particularly in IgAN patients, plasma CD147 levels were correlated with injured regions comprising more than 50% of glomeruli or with tubular atrophy/interstitial injury in biopsy tissues. Proteinuria showed a closer correlation with urinary values of CD147 and L-FABP. Of note, plasma and urinary CD147 levels showed a strong correlation with eGFR or proteinuria, respectively, only in DKD patients. Evaluation of plasma and urinary CD147 levels might provide key insights for the understanding of the activity of various kidney diseases.

Mean platelet volume is decreased in adults with active lupus disease.

PubMed

Delgado-García, Guillermo; Galarza-Delgado, Dionicio Ángel; Colunga-Pedraza, Iris; Borjas-Almaguer, Omar David; Mandujano-Cruz, Ilse; Benavides-Salgado, Daniel; Martínez-Granados, Rolando Jacob; Atilano-Díaz, Alexandro

2016-02-26

Only a few biomarkers are available for assessing disease activity in systemic lupus erythematosus (SLE). Mean platelet volume (MPV) has been recently studied as an inflammatory biomarker. It is currently unclear whether MPV may also play a role as a biomarker of disease activity in adult patients with SLE. We investigated the association between MPV and disease activity in adult patients with SLE. In this retrospective study, we compared two groups of adult patients divided according to disease activity (36 per group). Subjects were age- and gender-matched. MPV was significantly decreased with respect to those of inactive patients (7.16±1.39 vs. 8.16±1.50, p=0.005). At a cutoff level of 8.32 fL, MPV has a sensitivity of 86% and a specificity of 41% for the detection of disease activity. A modest positive correlation was found between MPV and albumin (r=0.407, p=0.001), which in turn is inversely associated with disease activity. In summary, MPV is decreased in adult patients with active lupus disease, and positively correlated with albumin, another biomarker of disease activity. Prospective studies are needed to evaluate the prognostic value of this biomarker. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Mean platelet volume is decreased in adults with active lupus disease.

PubMed

Delgado-García, Guillermo; Galarza-Delgado, Dionicio Ángel; Colunga-Pedraza, Iris; Borjas-Almaguer, Omar David; Mandujano-Cruz, Ilse; Benavides-Salgado, Daniel; Martínez-Granados, Rolando Jacob; Atilano-Díaz, Alexandro

Only a few biomarkers are available for assessing disease activity in systemic lupus erythematosus (SLE). Mean platelet volume (MPV) has been recently studied as an inflammatory biomarker. It is currently unclear whether MPV may also play a role as a biomarker of disease activity in adult patients with SLE. We investigated the association between MPV and disease activity in adult patients with SLE. In this retrospective study, we compared two groups of adult patients divided according to disease activity (36 per group). Subjects were age- and gender-matched. MPV was significantly decreased with respect to those of inactive patients (7.16±1.39 vs. 8.16±1.50, p=0.005). At a cutoff level of 8.32fL, MPV has a sensitivity of 86% and a specificity of 41% for the detection of disease activity. A modest positive correlation was found between MPV and albumin (r=0.407, p=0.001), which in turn is inversely associated with disease activity. In summary, MPV is decreased in adult patients with active lupus disease, and positively correlated with albumin, another biomarker of disease activity. Prospective studies are needed to evaluate the prognostic value of this biomarker. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Physical activity and fatigue in chronic obstructive pulmonary disease - A population based study.

PubMed

Andersson, Mikael; Stridsman, Caroline; Rönmark, Eva; Lindberg, Anne; Emtner, Margareta

2015-08-01

In subjects with chronic obstructive pulmonary disease (COPD), symptoms of fatigue, concomitant heart disease and low physical activity levels are more frequently described than in subjects without COPD. However, there are no population-based studies addressing the relationship between physical activity, fatigue and heart disease in COPD. The aim was to compare physical activity levels among subjects with and without COPD in a population based study, and to evaluate if concomitant heart disease and fatigue was associated to physical activity. In this, 470 subjects with COPD and 659 subjects without COPD (non-COPD) participated in examinations including structured interview and spirometry. A ratio of the forced expiratory volume in one second (FEV1)/best of forced vital capacity (FVC) and vital capacity (VC) < 0.7 was used to define COPD. Physical activity was assessed with the International Physical Activity Questionnaire (IPAQ), and fatigue with the Functional Assessment of Chronic Illness Therapy - Fatigue scale (FACIT-F). The prevalence of low physical activity was higher among subjects with FEV1 < 80% predicted compared to non-COPD subjects (22.4% vs. 14.6%, p = 0.041). The factors most strongly associated with low physical activity in subjects with COPD were older age, OR 1.52, (95% CI 1.12-2.06), a history of heart disease, OR 2.11 (1.10-4.08), and clinically significant fatigue, OR 2.33 (1.31-4.13); while obesity was the only significant factor among non-COPD subjects, OR 2.26 (1.17-4.35). Physical activity levels are reduced when lung function is decreased below 80% of predicted, and the factors associated with low physical activity are different among subject with and without COPD. We propose that the presence of fatigue and heart disease are useful to evaluate when identifying subjects for pulmonary rehabilitation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of choroidal thickness in psoriasis using optical coherence tomography.

PubMed

Türkcü, Fatih Mehmet; Şahin, Alparslan; Yüksel, Harun; Akkurt, Meltem; Uçmak, Derya; Çınar, Yasin; Yıldırım, Adnan; Çaça, İhsan

2016-12-01

The purpose of this study was to evaluate choroidal thickness (CT) in patients with psoriasis using enhanced depth imaging optical coherence tomography (EDI-OCT) and to determine its relationship with psoriasis activity indices. In this prospective study, EDI-OCT images were obtained in consecutive patients with psoriasis and in age-gender-matched healthy individuals. Comprehensive ophthalmic examination and EDI-OCT evaluation were performed. CT was measured in the subfoveal area. Correlation analyses were performed to identify the relationship of the CT with disease duration and clinical disease activity score. In total, 65 individuals were evaluated in this study, 35 with psoriasis and 30 controls. The mean disease duration of the patients with psoriasis was 15.7 ± 8.8 years (0.3-34 years). There was no difference between groups with respect to age and gender (p = 0.695 and p = 0.628, respectively). Five of the 35 patients with psoriasis had anterior uveitis. None of the patients with psoriasis had signs of posterior uveitis. CT was significantly higher in the psoriasis group than that of control subjects (p < 0.001). The mean central foveal thickness was comparable between groups (p = 0.672). There was also no significant correlation between EDI-OCT, disease activity score, and disease duration (p < 0.05). Choroidal thickness is increased in psoriasis patients. Large serial and comparative studies are necessary to evaluate EDI-OCT, an examination that may be helpful in understanding the effects of psoriasis on the eye and its pathophysiology.

Usefulness of Enzyme-linked Immunosorbent Assay Using Recombinant BP180 and BP230 for Serodiagnosis and Monitoring Disease Activity of Bullous Pemphigoid

PubMed Central

Lee, Eui Hyung; Kim, Yeon Hee; Kim, Sinyoung; Kim, Song-ee

2012-01-01

Background Bullous pemphigoid (BP) is an autoimmune subepidermal bullous disease associated with autoantibodies against BP180 and BP230. Enzyme-linked immunosorbent assay (ELISA) is a sensitive tool for the detection of immunoglobulin G (IgG) anti-BP180 and anti-BP230 autoantibodies. Objective The aim of this study was to evaluate the usefulness of ELISA for diagnosing and monitoring the disease activity of BP. Methods We evaluated serum IgG levels of anti-BP180 and anti-BP230 autoantibodies in 47 BP patients, 16 epidermolysis bullosa aquisita patients, and 15 healthy volunteers using ELISA. Through retrospective review of the medical records, the clinical characteristics of BP including disease activity, duration, pruritus severity and peripheral blood eosinophil counts were assessed. Results The sensitivity of BP180 ELISA was 97.9%, BP230 ELISA 72.3%, and a combination of the two was 100%. The specificity of BP180 ELISA was 90.3%, BP230 ELISA 100%, and a combination of the two was 90.3%. BP180 ELISA scores showed strong associations with disease activity, pruritus severity, peripheral blood eosinophil counts, and disease duration, whereas BP230 ELISA scores did not. Conclusion BP180 and BP230 ELISAs are highly sensitive methods for the diagnosis of BP, and BP180 ELISA, in particular, is a sensitive tool for monitoring the disease activity of BP. PMID:22363155

Correlation of alkaline phosphatase activity to clinical parameters of inflammation in smokers suffering from chronic periodontitis.

PubMed

Grover, Vishakha; Malhotra, Ranjan; Kapoor, Anoop; Bither, Rupika; Sachdeva, Sonia

2016-01-01

Current clinical periodontal diagnostic techniques emphasize the assessment of clinical and radiographic signs of periodontal diseases which can provide a measure of history of disease. Hence, new methodologies for early identification and determination of periodontal disease activity need to be explored which will eventually result in expedited treatment. To evaluate the correlation of alkaline phosphatase (ALP) activity in gingival crevicular fluid (GCF) to clinical parameters of periodontal inflammation in smokers with chronic periodontitis. Study population included 15 smoker male patients in the age group of 35-55 years suffering from moderate generalized chronic periodontitis with history of smoking present. Following parameters were evaluated at baseline, 1 month and 3 months after scaling and root planing: plaque index, bleeding index, probing pocket depth (PD), relative attachment level (RAL), and GCF ALP activity. Independent variables for measurements over time were analyzed by using Wilcoxon signed rank test. A statistically significant reduction in all the clinical parameters and GCF ALP activity was observed from baseline to 1 month and 3 months. A correlation was observed between change in GCF ALP activity and PD reduction as well as gain in RAL at 3 months. The present study emphasizes that total ALP activity could be used as a marker for periodontal disease activity in smokers. Estimation of changes in the levels of this enzyme has a potential to aid in the detection of progression of periodontal disease and monitoring the response to periodontal therapy.

Circulating anti-double-stranded DNA antibody-secreting cells in patients with systemic lupus erythematosus: a novel biomarker for disease activity.

PubMed

Hanaoka, H; Okazaki, Y; Satoh, T; Kaneko, Y; Yasuoka, H; Seta, N; Kuwana, M

2012-10-01

Antibodies against double-stranded DNA (dsDNA) are widely used to diagnose systemic lupus erythematosus (SLE) and evaluate its activity in patients. This study was undertaken to examine the clinical utility of circulating anti-dsDNA antibody-secreting cells for evaluating SLE patients. Anti-dsDNA antibody-secreting cells quantified using an enzyme-linked immunospot assay were detected in the spleen, bone marrow and peripheral blood from MRL/lpr but not in control BALB/c mice. Circulating anti-dsDNA antibody-secreting cells were detected in 29 (22%) of 130 patients with SLE, but in none of 49 with non-SLE connective-tissue disease or 18 healthy controls. The presence of circulating anti-dsDNA antibody-secreting cells was associated with persistent proteinuria, high SLE disease activity index and systemic lupus activity measures, and a high serum anti-dsDNA antibody titre measured with an enzyme-linked immunosorbent assay. The positive predictive value for active disease was 48% for circulating anti-dsDNA antibody-secreting cells versus 17% for serum anti-dsDNA antibodies. A prospective cohort of patients with circulating anti-dsDNA antibodies and inactive SLE showed that the cumulative disease flare-free rate was significantly lower in patients with than without circulating anti-dsDNA antibody-secreting cells (p < 0.001). Circulating anti-dsDNA antibody-secreting cells are a useful biomarker for assessing disease activity in SLE patients.

Meta-analysis using individual patient data: efficacy and durability of topical alicaforsen for the treatment of active ulcerative colitis.

PubMed

Vegter, S; Tolley, K; Wilson Waterworth, T; Jones, H; Jones, S; Jewell, D

2013-08-01

The antisense ICAM-1 inhibitor alicaforsen has been studied in four phase 2 studies in ulcerative colitis (UC). Recruited patients varied as to the extent of their colitis and in the severity of disease at entry. To investigate the efficacy of alicaforsen enema in specific UC populations. Efficacy was analysed for short-term (week 6-10) and long-term (week 30) outcomes compared with either placebo or a high-dose mesalazine (mesalamine) enema in patients with disease extent up to 40 cm from the anal verge in patients with moderate or severe disease, and in patients with both of these features. Individual patient data meta-analyses of 200 patients from four phase 2 studies evaluating nightly alicaforsen 240 mg enema and comparators. Patient data were pooled and analysed in a single data set. Continuous outcomes were evaluated using anova; dichotomous outcomes were evaluated using Pearson chi-square or Fisher's exact tests. Alicaforsen showed superior efficacy vs. placebo in: patients with disease extent up to 40 cm, patients with moderate and severe disease and especially when both those conditions were satisfied. In these patient groups, mesalazine also showed short-term efficacy. At week 30, however, the efficacy of mesalazine waned and alicaforsen became significantly more efficacious. This post hoc meta-analysis showed that alicaforsen is effective in patients with active UC, especially in patients with distal disease, which is of moderate/severe activity. The efficacy of alicaforsen was durable in these sub-groups, suggesting a disease-modifying effect. This analysis suggests that alicaforsen enema may offer an effective, potentially durable response in moderate/severe distal active UC. © 2013 John Wiley & Sons Ltd.

Fecal Calprotectin in Ileal Crohn's Disease: Relationship with Magnetic Resonance Enterography and a Pathology Score.

PubMed

Cerrillo, Elena; Beltrán, Belén; Pous, Salvador; Echarri, Ana; Gallego, Jose Carlos; Iborra, Marisa; Pamies, Jose; Nos, Pilar

2015-07-01

Magnetic resonance enterography (MRE) is an effective method of assessing small bowel Crohn's disease (CD). Fecal calprotectin (FC) correlates well with endoscopic disease activity. We aimed to evaluate the correlation between FC and disease activity according to MRE and surgical pathology in small bowel CD. One hundred twenty consecutive patients with ileal CD who underwent MRE assessment were included. Clinical data, C-reactive protein and FC, radiological and histological variables were obtained. Clinical activity was evaluated by the Harvey-Bradshaw Index and FC by enzyme-linked immunosorbent assay. MRE activity was assessed by means of the Magnetic Resonance Index of Activity score. Chiorean's score was used to grade pathological inflammation in surgical specimens. Seventy-five patients (62.5%) were in clinical remission (Harvey-Bradshaw Index < 5) and 45 (37.5%) had active disease (Harvey-Bradshaw Index ≥ 5). The Magnetic Resonance Index of Activity score was significantly associated with FC levels (P < 0.01), with a moderate overall correlation (Spearman's r = 0.56, P < 0.001). FC reflected MRE inflammatory activity with an area under the receiver operating characteristic curve of 0.914 (confidence interval, 0.849-0.958; P < 0.001). A cutoff value of 166.50 μg/g had 90% sensitivity, 74% specificity, 89% positive predictive value, and 76% negative predictive value for diagnosis of inflammation. Twenty-eight of 120 patients were operated. Surgical pathology showed a good agreement with FC for moderate (P = 0.03) and severe (P = 0.01) Chiorean's index. No relationship was detected for C-reactive protein. FC correlates with the degree of MRE inflammatory activity and with surgical pathology damage in ileal CD. Thus, FC could be a surrogate marker of disease control used to select patients for MRE assessment and therapeutic adjustment.

Stochastic agent-based modeling of tuberculosis in Canadian Indigenous communities.

PubMed

Tuite, Ashleigh R; Gallant, Victor; Randell, Elaine; Bourgeois, Annie-Claude; Greer, Amy L

2017-01-13

In Canada, active tuberculosis (TB) disease rates remain disproportionately higher among the Indigenous population, especially among the Inuit in the north. We used mathematical modeling to evaluate how interventions might enhance existing TB control efforts in a region of Nunavut. We developed a stochastic, agent-based model of TB transmission that captured the unique household and community structure. Evaluated interventions included: (i) rapid treatment of active cases; (ii) rapid contact tracing; (iii) expanded screening programs for latent TB infection (LTBI); and (iv) reduced household density. The outcomes of interest were incident TB infections and total diagnosed active TB disease over a 10- year time period. Model-projected incidence in the absence of additional interventions was highly variable (range: 33-369 cases) over 10 years. Compared to the 'no additional intervention' scenario, reducing the time between onset of active TB disease and initiation of treatment reduced both the number of new TB infections (47% reduction, relative risk of TB = 0.53) and diagnoses of active TB disease (19% reduction, relative risk of TB = 0.81). Expanding general population screening was also projected to reduce the burden of TB, although these findings were sensitive to assumptions around the relative amount of transmission occurring outside of households. Other potential interventions examined in the model (school-based screening, rapid contact tracing, and reduced household density) were found to have limited effectiveness. In a region of northern Canada experiencing a significant TB burden, more rapid treatment initiation in active TB cases was the most impactful intervention evaluated. Mathematical modeling can provide guidance for allocation of limited resources in a way that minimizes disease transmission and protects population health.

MS disease activity in RESTORE

PubMed Central

Cree, Bruce A.C.; De Sèze, Jerome; Gold, Ralf; Hartung, Hans-Peter; Jeffery, Douglas; Kappos, Ludwig; Kaufman, Michael; Montalbán, Xavier; Weinstock-Guttman, Bianca; Anderson, Britt; Natarajan, Amy; Ticho, Barry; Duda, Petra

2014-01-01

Objective: RESTORE was a randomized, partially placebo-controlled exploratory study evaluating multiple sclerosis (MS) disease activity during a 24-week interruption of natalizumab. Methods: Eligible patients were relapse-free through the prior year on natalizumab and had no gadolinium-enhancing lesions on screening brain MRI. Patients were randomized 1:1:2 to continue natalizumab, to switch to placebo, or to receive alternative immunomodulatory therapy (other therapies: IM interferon β-1a [IM IFN-β-1a], glatiramer acetate [GA], or methylprednisolone [MP]). During the 24-week randomized treatment period, patients underwent clinical and MRI assessments every 4 weeks. Results: Patients (n = 175) were randomized to natalizumab (n = 45), placebo (n = 42), or other therapies (n = 88: IM IFN-β-1a, n = 17; GA, n = 17; MP, n = 54). Of 167 patients evaluable for efficacy, 49 (29%) had MRI disease activity recurrence: 0/45 (0%) natalizumab, 19/41 (46%) placebo, 1/14 (7%) IM IFN-β-1a, 8/15 (53%) GA, and 21/52 (40%) MP. Relapse occurred in 4% of natalizumab patients and in 15%–29% of patients in the other treatment arms. MRI disease activity recurred starting at 12 weeks (n = 3 at week 12) while relapses were reported as early as 4–8 weeks (n = 2 in weeks 4–8) after the last natalizumab dose. Overall, 50/167 patients (30%), all in placebo or other-therapies groups, restarted natalizumab early because of disease activity. Conclusions: MRI and clinical disease activity recurred in some patients during natalizumab interruption, despite use of other therapies. Classification of evidence: This study provides Class II evidence that for patients with MS taking natalizumab who are relapse-free for 1 year, stopping natalizumab increases the risk of MS relapse or MRI disease activity as compared with continuing natalizumab. PMID:24682966

Disease activity, knee function, and walking ability in patients with rheumatoid arthritis 10 years after primary total knee arthroplasty.

PubMed

Nishikawa, Masataka; Owaki, Hajime; Takahi, Koichiro; Fuji, Takeshi

2014-04-01

To evaluate disease activity, knee function, and walking ability of patients with rheumatoid arthritis (RA) over 10 years after total knee arthroplasty (TKA). Four men and 26 women (mean age, 59.9 years) underwent 42 TKAs for RA with a mean duration of 151.3 months and were followed up for a mean of 142.3 months. Preoperatively, disease activity was assessed by C-reactive protein (CRP) level only, and the range of knee motion was recorded. At the final follow-up, tender joint count, swollen joint count, visual analogue scale of RA symptoms, and the Modified Health Assessment Questionnaire (MHAQ) score were assessed. Disease activity was evaluated using CRP, matrix metalloproteinase-3, and Disease Activity Score. Range of motion and Knee Society knee and function scores were also assessed. The use of methotrexate increased from 4 patients preoperatively to 20 patients at the final follow-up (p<0.001), and the mean dose increased from 3.9 to 6.3 mg/week (p<0.001). Among the 30 patients, the mean CRP level decreased from 2.63 mg/dl preoperatively to 0.61 mg/dl at the final follow-up (p<0.001). Disease activity was controlled. At the final follow-up, disease activity was in remission in 10 patients, low in 11, and moderate in 9. The mean Knee Society knee score was excellent (91.0), but the mean function score was poor (57.0) and diverse. Severe walking disability (function score, <40) was noted in 8 patients (11 TKAs). Knee and function scores did not correlate. Walking ability in patients with RA after TKA was generally poor. Poor function was associated with a history of spinal or lower extremity fracture surgery and the MHAQ score.

MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study.

PubMed

Fox, Robert J; Cree, Bruce A C; De Sèze, Jerome; Gold, Ralf; Hartung, Hans-Peter; Jeffery, Douglas; Kappos, Ludwig; Kaufman, Michael; Montalbán, Xavier; Weinstock-Guttman, Bianca; Anderson, Britt; Natarajan, Amy; Ticho, Barry; Duda, Petra

2014-04-29

RESTORE was a randomized, partially placebo-controlled exploratory study evaluating multiple sclerosis (MS) disease activity during a 24-week interruption of natalizumab. Eligible patients were relapse-free through the prior year on natalizumab and had no gadolinium-enhancing lesions on screening brain MRI. Patients were randomized 1:1:2 to continue natalizumab, to switch to placebo, or to receive alternative immunomodulatory therapy (other therapies: IM interferon β-1a [IM IFN-β-1a], glatiramer acetate [GA], or methylprednisolone [MP]). During the 24-week randomized treatment period, patients underwent clinical and MRI assessments every 4 weeks. Patients (n = 175) were randomized to natalizumab (n = 45), placebo (n = 42), or other therapies (n = 88: IM IFN-β-1a, n = 17; GA, n = 17; MP, n = 54). Of 167 patients evaluable for efficacy, 49 (29%) had MRI disease activity recurrence: 0/45 (0%) natalizumab, 19/41 (46%) placebo, 1/14 (7%) IM IFN-β-1a, 8/15 (53%) GA, and 21/52 (40%) MP. Relapse occurred in 4% of natalizumab patients and in 15%-29% of patients in the other treatment arms. MRI disease activity recurred starting at 12 weeks (n = 3 at week 12) while relapses were reported as early as 4-8 weeks (n = 2 in weeks 4-8) after the last natalizumab dose. Overall, 50/167 patients (30%), all in placebo or other-therapies groups, restarted natalizumab early because of disease activity. MRI and clinical disease activity recurred in some patients during natalizumab interruption, despite use of other therapies. This study provides Class II evidence that for patients with MS taking natalizumab who are relapse-free for 1 year, stopping natalizumab increases the risk of MS relapse or MRI disease activity as compared with continuing natalizumab.

Evaluating a Chronic Disease Management Improvement Collaboration: Lessons in Design and Implementation Fundamentals.

PubMed

Phillips, Kaye; Amar, Claudia; Elicksen-Jensen, Keesa

2016-01-01

For the Canadian Foundation for Healthcare Improvement (CFHI), the Atlantic Healthcare Collaboration (AHC) was a pivotal opportunity to build upon its experience and expertise in delivering regional change management training and to apply and refine its evaluation and performance measurement approach. This paper reports on its evaluation principles and approach, as well as the lessons learned as CFHI diligently coordinated and worked with improvement project (IP) teams and a network of stakeholders to design and undertake a suite of evaluative activities. The evaluation generated evidence and learnings about various elements of chronic disease prevention and management (CDPM) improvement processes, individual and team capacity building and the role and value of CFHI in facilitating tailored learning activities and networking among teams, coaches and other AHC stakeholders.

Association of weight loss with improved disease activity in patients with rheumatoid arthritis: A retrospective analysis using electronic medical record data

PubMed Central

Kreps, David J.; Halperin, Florencia; Desai, Sonali P.; Zhang, Zhi Z.; Losina, Elena; Olson, Amber T.; Karlson, Elizabeth W.; Bermas, Bonnie L.; Sparks, Jeffrey A.

2018-01-01

Objective To evaluate the association between weight loss and rheumatoid arthritis (RA) disease activity. Methods We conducted a retrospective cohort study of RA patients seen at routine clinic visits at an academic medical center, 2012–2015. We included patients who had ≥2 clinical disease activity index (CDAI) measures. We identified visits during follow-up where the maximum and minimum weights occurred and defined weight change and CDAI change as the differences of these measures at these visits. We defined disease activity improvement as CDAI decrease of ≥5 and clinically relevant weight loss as ≥5 kg. We performed logistic regression analyses to establish the association between improved disease activity and weight loss and baseline BMI category (≥25 kg/m2 or <25 kg/m2). We built linear regression models to investigate the association between continuous weight loss and CDAI change among patients who were overweight/obese at baseline and who lost weight during follow-up. Results We analyzed data from 174 RA patients with a median follow-up of 1.9 years (IQR 1.3–2.4); 117 (67%) were overweight/obese at baseline, and 53 (31%) lost ≥5 kg during follow-up. Patients who were overweight/obese and lost ≥5 kg had three-fold increased odds of disease activity improvement compared to those who did not (OR 3.03, 95%CI 1.18–7.83). Among those who were overweight/obese at baseline, each kilogram weight loss was associated with CDAI improvement of 1.15 (95%CI 0.42–1.88). Our study was limited by using clinical data from a single center without fixed intervals for assessments. Conclusion Clinically relevant weight loss (≥5 kg) was associated with improved RA disease activity in the routine clinical setting. Further studies are needed for replication and to evaluate the effect of prospective weight loss interventions on RA disease activity. PMID:29606976

Development of the Korean Academy of Medical Sciences Guideline for Rating the Impairment in the Brain Injured and Brain Diseased Persons with Motor Dysfunction

PubMed Central

Baik, Jong Sam; Jang, Seong Ho; Park, Dong Sik

2009-01-01

To develop an objective and scientific method to evaluate the brain injured and brain diseased persons with motor dysfunction, American Medical Association's Guides to the Evaluation of Permanent Impairment was used as an exemplar. After the motor dysfunction due to brain injury or brain disease was confirmed, active range of motion and muscle strength of affected extremities were measured. Also, the total function of extremities was evaluated through the assessment of activities of daily living, fine coordination of hand, balance and gait. Then, the total score of manual muscle test and functional assessment of impaired upper and lower extremity were added, respectively. Spasticity of upper and lower extremity was used as minus factors. Patients with movement disorder such as Parkinson's disease were assessed based on the degree of dysfunction in response to medication. We develop a new rating system based on the concept of total score. PMID:19503680

Ileal Crohn disease: mural microvascularity quantified with contrast-enhanced US correlates with disease activity.

PubMed

De Franco, Antonio; Di Veronica, Alessandra; Armuzzi, Alessandro; Roberto, Italia; Marzo, Manuela; De Pascalis, Barbara; De Vitis, Italo; Papa, Alfredo; Bock, Enrico; Danza, Francesco M; Bonomo, Lorenzo; Guidi, Luisa

2012-02-01

To quantitatively assess microvascular activation in the thickened ileal walls of patients with Crohn disease (CD) by using contrast-enhanced ultrasonography (US) and evaluate its correlation with widely used indexes of CD activity. This prospective study was approved by the ethics committee, and written informed consent was obtained from all patients. The authors examined 54 consecutively enrolled patients (mean age, 35.29 years; age range, 18-69 years; 39 men, 15 women) with endoscopically confirmed CD of the terminal ileum. Ileal wall segments thicker than 3 mm were examined with low-mechanical-index contrast-enhanced US and a second-generation US contrast agent. The authors analyzed software-plotted time-enhancement intensity curves to determine the maximum peak intensity (MPI) and wash-in slope coefficient (β) and evaluated their correlation with (a) the composite index of CD activity (CICDA), (b) the CD activity index (CDAI), and (c) the simplified endoscopic score for CD (SES-CD, evaluated in 37 patients) for the terminal ileum. Statistical analysis was performed with the Mann-Whitney test, Spearman rank test, and receiver operating characteristic (ROC) analysis. MPI and β coefficients were significantly increased in the 36 patients with a CICDA indicative of active disease (P<.0001 for both), the 33 patients with a CDAI of at least 150 (P<.032 and P<.0074, respectively), and the 26 patients with an SES-CD of at least 1 (P<.0001 and P<.002, respectively). ROC analysis revealed accurate identification (compared with CICDA) of active CD with an MPI threshold of 24 video intensity (VI) (sensitivity, 97%; specificity, 83%) and a β coefficient of 4.5 VI/sec (sensitivity, 86%; specificity, 83%). Contrast-enhanced US of the ileal wall is a promising method for objective, reproducible assessment of disease activity in patients with ileal CD. © RSNA, 2011

Project SuperHeart: An Evaluation of a Heart Disease Intervention Program For Children.

ERIC Educational Resources Information Center

Way, Joyce W.

1981-01-01

An effective way to prevent coronary heart disease in later life is to concentrate on preventive measures in the early years before coronary heart disease becomes established. Project SuperHeart, a heart disease intervention program for young children, includes physical fitness and classroom activities emphasizing basic nutritional habits. (JN)

Synthesis and bioevaluation of new tacrine-cinnamic acid hybrids as cholinesterase inhibitors against Alzheimer's disease.

PubMed

Chen, Yao; Zhu, Jie; Mo, Jun; Yang, Hongyu; Jiang, Xueyang; Lin, Hongzhi; Gu, Kai; Pei, Yuqiong; Wu, Liang; Tan, Renxiang; Hou, Jing; Chen, Jingyi; Lv, Yang; Bian, Yaoyao; Sun, Haopeng

2018-12-01

Small molecule cholinesterases inhibitor (ChEI) provides an effective therapeutic strategy to treat Alzheimer's disease (AD). Currently, the discovery of new ChEI with multi-target effect is still of great importance. Herein, we report the synthesis, structure-activity relationship study and biological evaluation of a series of tacrine-cinnamic acid hybrids as new ChEIs. All target compounds are evaluated for their in vitro cholinesterase inhibitory activities. The representatives which show potent activity on cholinesterase, are evaluated for the amyloid β-protein self-aggregation inhibition and in vivo assays. The optimal compound 19, 27, and 30 (human AChE IC 50  = 10.2 ± 1.2, 16.5 ± 1.7, and 15.3 ± 1.8 nM, respectively) show good performance in ameliorating the scopolamine-induced cognition impairment and preliminary safety in hepatotoxicity evaluation. These compounds deserve further evaluation for the development of new therapeutic agents against AD.

Salicylanilide Inhibitors of Toxoplasma gondii

PubMed Central

Fomovska, Alina; Wood, Richard D.; Mui, Ernest; Dubey, Jitenter P.; Ferriera, Leandra R.; Hickman, Mark R.; Lee, Patricia J.; Leed, Susan E.; Auschwitz, Jennifer M.; Welsh, William J.; Sommerville, Caroline; Woods, Stuart; Roberts, Craig; McLeod, Rima

2012-01-01

Toxoplasma gondii(T. gondii) is an apicomplexan parasite that can cause eye disease, brain disease, and death, especially in congenitally infected and immune-compromised people. Novel medicines effective against both active and latent forms of the parasite are greatly needed. The current study focused on the discovery of such medicines by exploring a family of potential inhibitors whose anti-apicomplexan activity has not been previously reported. Initial screening efforts revealed that niclosamide, a drug approved for anthelmintic use, possessed promising activity in vitro against T. gondii. This observation inspired the evaluation of the activity of a series of salicylanilides and derivatives. Several inhibitors with activities in the nanomolar range with no appreciable in vitro toxicity to human cells were identified. An initial structure-activity relationship was explored. Four compounds were selected for evaluation in an in vivo model of infection, and two derivatives with potentially enhanced pharmacological parameters demonstrated the best activity profiles. PMID:22970937

A Comparitive Study of Anticardiolipin Antibodies among Systemic Lupus Erythematosus Patients from Western and Eastern India.

PubMed

Doley, D; Kakati, S; Saikia, L; Rajadhyaksha, A; Nadkar, Milind; Khadilkar, P; Patwardhan, M; Pradhan, V

2017-03-01

Anti-phospholipid antibodies (APA) like anticardiolipin antibodies (ACA) are important cause of venous and arterial thrombosis and other occlusive vascular diseases. Prevalence of these antibodies in SLE patients at the time of diagnosis is not known in Indian SLE patients. This study was conducted to evaluate the prevalence of ACA in SLE patients from Eastern and Western India and to correlate them with disease activity. Seventy SLE patients from Assam Medical College, Dibrugarh, Assam and 85 SLE patients from Rheumatology Department, KEM Hospital, Mumbai were studied. SLE disease activity was evaluated by SLE Disease Activity Index (SLEDAI) score at the time of evaluation. All patients studied were in an active stage of disease. Demographic data showed significant variations in the clinical manifestations of SLE between two regions. Renal manifestations were higher (42.9%) among SLE patients from Eastern region as compared with 37.6% patients from Western region. These patients were categorized as Lupus Nephritis (LN) and patients that did not show any renal manifestations were categories as non-LN. ACA to IgG and IgM subclasses were tested by ELISA. IgGACA positivity was 20%, 12.9% and IgM-ACA positivity was 18.6%, 12.9% where asIgG + IgM ACA positivity as found in 12.9%, 3.5% patients respectively among SLE patients from Eastern and Western India. ACA positivity was higher among LN patients from Eastern India whereas the same was higher among non-LN patients from Western India. Hence detection of ACA alongwith associated clinical manifestations were helpful to evaluate their possible association with disease severity in SLE patients. A long term follow up of patients having ACA antibodies without thrombotic event is needed to detect their possible thrombotic event in future along with their clinical presentation from these two different geographic regions from India.

Antismooth muscle and antiactin antibodies are indirect markers of histological and biochemical activity of autoimmune hepatitis.

PubMed

Couto, Claudia A; Bittencourt, Paulo L; Porta, Gilda; Abrantes-Lemos, Clarice P; Carrilho, Flair J; Guardia, Bianca D; Cançado, Eduardo L R

2014-02-01

Reactivity and titers of autoantibodies vary during the course of autoimmune hepatitis (AIH), and some autoantibodies have been associated with disease activity and adverse outcomes after treatment. The aim of this study was to assess the autoantibody behavior in AIH and its significance as predictors of biochemical and histological remission. A total of 117 patients with AIH (mean age 18.6 [4-69] years) were evaluated and tested for autoantibodies at disease onset and successively (mean 3.2 [2-6] times) after a mean follow-up evaluation of 70 [20-185] months. Antismooth muscle (ASMA), antiliver kidney microsome type 1 (anti-LKM1), antiliver cytosol type 1 (anti-LC1), antimitochondrial, antinuclear (ANA), and antiactin antibodies (AAA) were determined at disease onset and 379 other times during the follow-up evaluation through indirect immunofluorescence in rodent tissues, HEp-2 cells, and human fibroblasts. Anti-SLA/LP were assessed 45 times in the follow-up evaluation of 19 patients using enzyme-linked immunosorbent assay (ELISA). Upon admission, AIH types 1 and 2 were observed in 95 and 17 patients, respectively. Five subjects had AIH with anti-SLA/LP as the sole markers. Patients initially negative for AAA did not develop these antibodies thereafter. ANA were detected de novo in six and three subjects with AIH types 1 and 2, respectively. After treatment, only ASMA (>1:80) and AAA (>1:40) were significantly associated with biochemical (76.9% and 79.8%) and histological features (100% and 100%) of disease activity (P < 0.001). With the exception of ANA, the autoantibody profile does not markedly vary in the course of AIH. The persistence of high titers of ASMA and/or AAA in patients with AIH is associated with disease activity. © 2013 by the American Association for the Study of Liver Diseases.

Resilience in women with autoimmune rheumatic diseases.

PubMed

Rojas, Manuel; Rodriguez, Yhojan; Pacheco, Yovana; Zapata, Elizabeth; Monsalve, Diana M; Mantilla, Rubén D; Rodríguez-Jimenez, Monica; Ramírez-Santana, Carolina; Molano-González, Nicolás; Anaya, Juan-Manuel

2017-12-28

To evaluate the relationship between resilience and clinical outcomes in patients with autoimmune rheumatic diseases. Focus groups, individual interviews, and chart reviews were done to collect data on 188 women with autoimmune rheumatic diseases, namely rheumatoid arthritis (n=51), systemic lupus erythematosus (n=70), systemic sclerosis (n=35), and Sjögren's syndrome (n=32). Demographic, clinical, and laboratory variables were assessed including disease activity by patient reported outcomes. Resilience was evaluated by using the Brief Resilience Scale. Bivariate, multiple linear regression, and classification and regression trees were used to analyse data. Resilience was influenced by age, duration of disease, and socioeconomic status. Lower resilience scores were observed in younger patients (<48years) with systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis who had low socioeconomic status, whereas older patients (>50years) had higher resilience scores regardless of socioeconomic status. There was no influence of disease activity on resilience. A particular behaviour was observed in systemic sclerosis in which patients with high socioeconomic status and regular physical activity had higher resilience scores. Resilience in patients with autoimmune rheumatic diseases is a continuum process influenced by age and socioeconomic status. The ways in which these variables along with exercise influence resilience deserve further investigation. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Efficacy of noninvasive evaluations in monitoring inflammatory bowel disease activity: A prospective study in China

PubMed Central

Chen, Jin-Min; Liu, Tao; Gao, Shan; Tong, Xu-Dong; Deng, Fei-Hong; Nie, Biao

2017-01-01

AIM To optimize the efficacy of noninvasive evaluations in monitoring the endoscopic activity of inflammatory bowel disease (IBD). METHODS Fecal calprotectin (FC), clinical activity index (CDAI or CAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT) were measured for 136 IBD patients. Also, FC was measured in 25 irritable bowel syndrome (IBS) patients that served as controls. Then, endoscopic activity was determined by other two endoscopists for colonic or ileo-colonic Crohn’s disease (CICD) with the “simple endoscopic score for Crohn’s disease” (SES-CD), CD-related surgery patients with the Rutgeerts score, and ulcerative colitis (UC) with the Mayo score. The efficacies of these evaluations to predict the endoscopic disease activity were assessed by Mann-Whitney test, χ2 test, Spearman’s correlation, and multiple linear regression analysis. RESULTS The median FC levels in CD, UC, and IBS patients were 449.6 (IQR, 137.9-1344.8), 497.9 (IQR, 131.7-118.0), and 9.9 (IQR, 049.7) μg/g, respectively (P < 0.001). For FC, CDAI or CAI, CRP, and ESR differed significantly between endoscopic active and remission in CICD and UC patients, but not in CD-related surgery patients. The SES-CD correlated closely with levels of FC (r = 0.802), followed by CDAI (r = 0.734), CRP (r = 0.658), and ESR (r = 0.557). The Mayo score also correlated significantly with FC (r = 0.837), CAI (r = 0.776), ESR (r = 0.644), and CRP (r = 0.634). For FC, a cut-off value of 250 μg/g indicated endoscopic active inflammation with accuracies of 87.5%, 60%, and 91.1%, respectively, for CICD, CD-related surgery, and UC patients. Moreover, clinical FC activity (CFA) calculated as 0.8 × FC + 4.6 × CDAI showed higher area under the curve (AUC) of 0.962 for CICD and CFA calculated as 0.2 × FC + 50 × CAI showed higher AUC (0.980) for UC patients than the FC. Also, the diagnostic accuracy of FC in identifying patients with mucosal inflammation in clinical remission was reflected by an AUC of 0.91 for CICD and 0.96 for UC patients. CONCLUSION FC is the most promising noninvasive evaluation for monitoring the endoscopic activity of CICD and UC. CFA might be more accurate for IBD activity evaluation. PMID:29290660

Unravelling effectiveness of a nurse-led behaviour change intervention to enhance physical activity in patients at risk for cardiovascular disease in primary care: study protocol for a cluster randomised controlled trial.

PubMed

Westland, Heleen; Bos-Touwen, Irene D; Trappenburg, Jaap C A; Schröder, Carin D; de Wit, Niek J; Schuurmans, Marieke J

2017-02-22

Self-management interventions are considered effective in patients with chronic disease, but trials have shown inconsistent results, and it is unknown which patients benefit most. Adequate self-management requires behaviour change in both patients and health care providers. Therefore, the Activate intervention was developed with a focus on behaviour change in both patients and nurses. The intervention aims for change in a single self-management behaviour, namely physical activity, in primary care patients at risk for cardiovascular disease. The aim of this study is to evaluate the effectiveness of the Activate intervention. A two-arm cluster randomised controlled trial will be conducted to compare the Activate intervention with care as usual at 31 general practices in the Netherlands. Approximately 279 patients at risk for cardiovascular disease will participate. The Activate intervention is developed using the Behaviour Change Wheel and consists of 4 nurse-led consultations in a 3-month period, integrating 17 behaviour change techniques. The Behaviour Change Wheel was also applied to analyse what behaviour change is needed in nurses to deliver the intervention adequately. This resulted in 1-day training and coaching sessions (including 21 behaviour change techniques). The primary outcome is physical activity, measured as the number of minutes of moderate to vigorous physical activity using an accelerometer. Potential effect modifiers are age, body mass index, level of education, social support, depression, patient-provider relationship and baseline number of minutes of physical activity. Data will be collected at baseline and at 3 months and 6 months of follow-up. A process evaluation will be conducted to evaluate the training of nurses, treatment fidelity, and to identify barriers to and facilitators of implementation as well as to assess participants' satisfaction. To increase physical activity in patients and to support nurses in delivering the intervention, behaviour change techniques are applied to change behaviours of the patients and nurses. Evaluation of the effectiveness of the intervention, exploration of which patients benefit most, and evaluation of our theory-based training for primary care nurses will enhance understanding of what works and for whom, which is essential for further implementation of self-management in clinical practice. ClinicalTrials.gov identifier: NCT02725203 . Registered on 25 March 2016.

78 FR 17411 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-21

... announced below concerns Monitoring and Evaluation of Malaria Control and Elimination Activities, FOA GH13..., discussion, and evaluation of applications received in response to ``Monitoring and Evaluation of Malaria...

Quality of Life in Ecuadorian Patients With Rheumatoid Arthritis: A Cross-sectional Study.

PubMed

Cruz-Castillo, Yessenia; Montero, Nadia; Salazar-Ponce, Rosa; Villacís-Tamayo, Rómulo

2017-11-01

To evaluate health-related quality of life (HRQoL) and associated clinical, demographic and socioeconomic factors in a cohort of Ecuadorian patients with rheumatoid arthritis (RA). A cross-sectional descriptive study evaluating (HRQoL) with the Spanish version of the Quality of Life Rheumatoid Arthritis (QoL-RA) instrument in patients diagnosed with RA according to the criteria of the American College of Rheumatology and the European League Against Rheumatism. In addition, the following data were obtained: age, sex, marital status, socioeconomic stratum, comorbidities, disease duration, medication, rheumatoid factor positivity, disease activity using the simplified disease activity index and physical functionality measured with the modified Health Assessment Questionnaire (MHAQ). A total of 163 patients were assessed, the mean score of the QoL-RA scale was 6.84±1.5 points. The highest measurements were obtained in the domains of interaction (8.04±1.9) and support (8.01±2). The factors that were associated with the overall quality of life assessment were: functionality measured with MHAQ (r=-0.70; P<.001); disease duration in years (r=-0.178; P<.05); and disease activity (mean difference of 1.5; 95%CI: 1.09 to 1.91). The patients evaluated had a good to moderate HRQoL. The domains related to support and social life were those with the highest scores and the lowest scores were related to pain and nervous tension. Functionality, duration, and disease activity were statistically associated with HRQoL. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Evaluation of neopterin as a biomarker for the monitoring of Gaucher disease patients.

PubMed

Drugan, Cristina; Drugan, Tudor C; Miron, Nicolae; Grigorescu-Sido, Paula; Naşcu, Ioana; Cătană, Cristina

2016-07-01

Biomarker research is an important area of investigation in Gaucher disease, caused by an inherited deficiency of a lysosomal enzyme, glucocerebrosidase. We evaluated the usefulness of neopterin, as a novel biomarker reflecting chronic inflammation and immune system activation in Gaucher disease and analysed its evolution in response to enzyme replacement therapy (ERT). Circulating plasma neopterin levels in 31 patients with non-neuronopathic Gaucher disease were measured before and after the onset of ERT and were compared with those of 18 healthy controls. Plasma chitotriosidase activity was also monitored, as a reference biomarker, against which we evaluated the evolution of neopterin. Neopterin levels were significantly increased in treatment-naïve patients (mean 11.90 ± 5.82 nM) compared with controls (6.63 ± 5.59 nM, Mann-Whitney U test P = 0.001), but returned to normal levels (6.92 ± 4.66 nM) following ERT. Investigating the diagnostic value of neopterin by receiver operating characteristic analysis, we found a cut-off value of 7.613 nM that corresponds to an area under the curve of 0.780 and indicates a good discrimination capacity, with a sensitivity of 0.774 and a specificity of 0.778. Our results suggest that measurement of circulating neopterin may be considered as a novel test for the confirmation of diagnosis and monitoring of the efficacy of therapeutic intervention in Gaucher disease. Plasma neopterin levels reflect the global accumulation and activation of Gaucher cells and the extent of chronic immune activation in this disorder. Neopterin may be an alternative storage cell biomarker in Gaucher disease, especially in chitotriosidase-deficient patients.

Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

PubMed

Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-Scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-Guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; McCombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Luis Sanchez-Menoyo, Jose; Laura Saladino, Maria; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut

2017-09-01

Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of disability regression was predominantly associated with pre-baseline disability, therapy and relapse activity. Relapse incidence was associated with pretreatment relapse activity, age and relapsing disease course, with the strength of these associations varying among therapies. Accuracy and internal validity (n = 1196) of the resulting predictive models was high (>80%) for relapse incidence during the first year and for disability outcomes, moderate for relapse incidence in Years 2-4 and for the change in the cumulative disease burden, and low for conversion to secondary progressive disease and treatment discontinuation. External validation showed similar results, demonstrating high external validity for disability and relapse outcomes, moderate external validity for cumulative disease burden and low external validity for conversion to secondary progressive disease and treatment discontinuation. We conclude that demographic, clinical and paraclinical information helps predict individual response to disease-modifying therapies at the time of their commencement. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Retinol Binding Protein 4 in children with Inflammatory Bowel Disease: a negative correlation with the disease activity.

PubMed

Roma, E; Krini, M; Hantzi, E; Sakka, S; Panayiotou, I; Margeli, A; Papassotiriou, I; Kanaka-Gantenbein, C

2012-10-01

Retinol Binding Protein-4 (RBP-4), the action of which was initially thought to be only the transport of vitamin A, is a major circulating adipocytokine involved in the inflammation. We evaluated the serum RBP-4 levels in children with inflammatory bowel disease (IBD) and correlated them with transthyretin (TTR), inflammation markers, disease activity, and body mass index (BMI). In 41 children of mean age 11.9 ± 3.6 years (range 5-17.7 y) with IBD (19 with Crohn's disease (CD) and 22 with Ulcerative colitis (UC) serum RBP-4, TTR, Amyloid A (SAA), C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), disease activity and BMI were prospectively determined and compared with those of 42 matched controls. No difference in the RBP-4 and TTR serum levels, between patients and controls as well as between active and remission state of the disease was noticed. A negative correlation of serum RBP-4 with the disease activity, SAA and ESR and a positive correlation with TTR was found, but no significant correlation with CRP or BMI was found. Inflammation markers were significantly increased in patients compared to controls and had a positive correlation with the disease activity. RBP-4 negatively correlated with disease activity of children with IBD probably indicating a protective anti-inflammatory mechanism of action in addition to transport of vitamin A.

Structure-Based Design, Synthesis, Biological Evaluation, and Molecular Docking of Novel PDE10 Inhibitors with Antioxidant Activities

NASA Astrophysics Data System (ADS)

Li, Jinxuan; Chen, Jing-Yi; Deng, Ya-Lin; Zhou, Qian; Wu, Yinuo; Wu, Deyan; Luo, Hai-Bin

2018-05-01

Phosphodiesterase 10 is a promising target for the treatment of a series of central nervous system (CNS) diseases. Imbalance between oxidative stress and antioxidant defense systems as a universal condition in neurodegenerative disorders is widely studied as a potential therapy for CNS diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). To discover multifunctional pharmaceuticals as a treatment for neurodegenerative diseases, a series of quinazoline-based derivatives with PDE10 inhibitory activities and antioxidant activities were designed and synthesized. Nine out of thirteen designed compounds showed good PDE10 inhibition at the concentration of 1.0 μM. Among these compounds, eight exhibited moderate to excellent antioxidant activity with ORAC (oxygen radical absorbance capacity) value above 1.0. Molecular docking was performed for better understanding of the binding patterns of these compounds with PDE10. Compound 11e, which showed remarkable inhibitory activity against PDE10 and antioxidant activity may serve as a lead for the further modification.

Increased Disease Activity is Associated with Altered Sleep Architecture in an Experimental Model of Systemic Lupus Erythematosus

PubMed Central

Palma, Beatriz Duarte; Tufik, Sergio

2010-01-01

Study Objectives: The aim of this study was to evaluate sleep patterns during the course of the disease in (NZB/NZW)F1 mice, an experimental model of systemic lupus erythematosus (SLE). Design: Female mice were implanted with electrodes for chronic recording of sleep-wake cycles during the entire experimental phase (9, 19, and 29 weeks of age). The disease course was also assessed. At each time-point, blood samples were collected from the orbital plexus to evaluate serum antinuclear antibodies (ANA), which are important serologic parameters of disease evolution. Pain perception was also evaluated. Measurements and Results: During the dark phase, (NZB/NZW)F1 mice aged 19 weeks spent more time in sleep, and, as a consequence, the total waking time was lower when compared with earlier periods. An augmented number of sleep-stage transitions and microarousals were observed at the 29th week of life in both light and dark phases. At this same time-point, the mice showed lower pain thresholds than they had at 9 weeks of life. The disease status was confirmed; the entire group of mice at 29 weeks of life showed positive ANA with high titer levels. Conclusions: The sleep-recording data showed that, during the progress and severe phases of the disease (19 and 29 wks of age, respectively), sleep architecture is altered. According to these results, increased sleep fragmentation, disease activity, and pain sensitivity are features observed in these mice, similar to symptoms of SLE. Citation: Palma BD; Tufik S. Increased disease activity is associated with altered sleep architecture in an experimental model of systemic lupus erythematosus. SLEEP 2010;33(9):1244-1248. PMID:20857872

Strengths, Limitations, and Geographical Discrepancies in the Eligibility Criteria for Sport Participation in Young Patients With Congenital Heart Disease.

PubMed

Cantinotti, Massimiliano; Giordano, Raffaele; Assanta, Nadia; Murzi, Bruno; Melo, Manuel; Franchi, Eliana; Crocetti, Maura; Iervasi, Giorgio; Kutty, Shelby

2017-07-21

Benefits of physical activity has been shown in children with congenital heart disease (CHD). In several forms of CHD, the risk of sudden death remains a major concern both for parents and clinicians, who in turn will have to consider the risk-benefit ratio of sport participation versus restriction. A literature search was performed within the National Library of Medicine using the keywords: Sport, CHD, and Eligibility. The search was further refined by adding the keywords: Children, Adult, and Criteria. Fifteen published studies evaluating sport eligibility criteria in CHD were included. Seven documents from various scientific societies have been published in the past decade but which of them should be adopted remains unclear. Our research highlighted accuracy and consistency of the latest documents; however, differences have emerged between the US and European recommendations. Eligibility criteria were consistent between countries for simple congenital heart defects, whereas there are discrepancies for borderline conditions including moderate valvular lesions and mild or moderate residual defects after CHD repair. Furthermore, some of the more severe defects were not evaluated. Multiple recommendations have been made for the same CHD, and cut-off values used to define disease severity have varied. Published eligibility criteria have mainly focused on competitive sports. Little attention was paid to recreational activities, and the psychosocial consequences of activity restriction were seldom evaluated. Comprehensive consensus recommendations for sport eligibility evaluating all CHD types and stages of repair are needed. These should include competitive and recreational activities, use standardized classifications to grade disease severity, and address the consequences of restriction.

Beyond endoscopic assessment in inflammatory bowel disease: real-time histology of disease activity by non-linear multimodal imaging

NASA Astrophysics Data System (ADS)

Chernavskaia, Olga; Heuke, Sandro; Vieth, Michael; Friedrich, Oliver; Schürmann, Sebastian; Atreya, Raja; Stallmach, Andreas; Neurath, Markus F.; Waldner, Maximilian; Petersen, Iver; Schmitt, Michael; Bocklitz, Thomas; Popp, Jürgen

2016-07-01

Assessing disease activity is a prerequisite for an adequate treatment of inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis. In addition to endoscopic mucosal healing, histologic remission poses a promising end-point of IBD therapy. However, evaluating histological remission harbors the risk for complications due to the acquisition of biopsies and results in a delay of diagnosis because of tissue processing procedures. In this regard, non-linear multimodal imaging techniques might serve as an unparalleled technique that allows the real-time evaluation of microscopic IBD activity in the endoscopy unit. In this study, tissue sections were investigated using the non-linear multimodal microscopy combination of coherent anti-Stokes Raman scattering (CARS), two-photon excited auto fluorescence (TPEF) and second-harmonic generation (SHG). After the measurement a gold-standard assessment of histological indexes was carried out based on a conventional H&E stain. Subsequently, various geometry and intensity related features were extracted from the multimodal images. An optimized feature set was utilized to predict histological index levels based on a linear classifier. Based on the automated prediction, the diagnosis time interval is decreased. Therefore, non-linear multimodal imaging may provide a real-time diagnosis of IBD activity suited to assist clinical decision making within the endoscopy unit.

ACE phenotyping in Gaucher disease.

PubMed

Danilov, Sergei M; Tikhomirova, Victoria E; Metzger, Roman; Naperova, Irina A; Bukina, Tatiana M; Goker-Alpan, Ozlem; Tayebi, Nahid; Gayfullin, Nurshat M; Schwartz, David E; Samokhodskaya, Larisa M; Kost, Olga A; Sidransky, Ellen

2018-04-01

Gaucher disease is characterized by the activation of splenic and hepatic macrophages, accompanied by dramatically increased levels of angiotensin-converting enzyme (ACE). To evaluate the source of the elevated blood ACE, we performed complete ACE phenotyping using blood, spleen and liver samples from patients with Gaucher disease and controls. ACE phenotyping included 1) immunohistochemical staining for ACE; 2) measuring ACE activity with two substrates (HHL and ZPHL); 3) calculating the ratio of the rates of substrate hydrolysis (ZPHL/HHL ratio); 4) assessing the conformational fingerprint of ACE by evaluating the pattern of binding of monoclonal antibodies to 16 different ACE epitopes. We show that in patients with Gaucher disease, the dramatically increased levels of ACE originate from activated splenic and/or hepatic macrophages (Gaucher cells), and that both its conformational fingerprint and kinetic characteristics (ZPHL/HHL ratio) differ from controls and from patients with sarcoid granulomas. Furthermore, normal spleen was found to produce high levels of endogenous ACE inhibitors and a novel, tightly-bound 10-30 kDa ACE effector which is deficient in Gaucher spleen. The conformation of ACE is tissue-specific. In Gaucher disease, ACE produced by activated splenic macrophages differs from that in hepatic macrophages, as well as from macrophages and dendritic cells in sarcoid granulomas. The observed differences are likely due to altered ACE glycosylation or sialylation in these diseased organs. The conformational differences in ACE may serve as a specific biomarker for Gaucher disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Activity of inflammatory bowel disease influences the expression of cytokines in gingival tissue.

PubMed

Figueredo, C M; Martins, A P; Lira-Junior, R; Menegat, J B; Carvalho, A T; Fischer, R G; Gustafsson, A

2017-07-01

This study assessed the cytokine expression in gingival and intestinal tissues from periodontitis patients with inflammatory bowel disease (IBD) and evaluated if IBD activity is a covariate to the amount of gingival cytokines. Paired gingival and intestinal tissues were collected from 21 patients and homogenised using a cell disruptor. Cytokine expression (IL-1β, IL-4, IL-6, IL-10, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IL-17A, IL-17F, IFN-γ, sCD40L, and TNF-α) was evaluated using bead-based multiplex technology. An inflammation score was developed using the intestinal cytokines that showed good accuracy to discriminate IBD active patients from those in remission and then a similar score was applied to gingival tissue. IL-4, IL-10 and IL-21 expressions were significantly increased in gingival tissue from patients with an active disease as compared to those with a disease in remission. The inflammation score (mean value of IL-1β, IL-6, IL-21, and sCD40L) was significantly higher in gingival tissue from patients with IBD activity. There was a significant correlation between gingival and intestinal inflammation scores (rho=0.548; P=0.01). Significantly higher IL-23 and IFN-γ levels and lower IL-31 and TNF-α levels were observed in gingival tissues than in intestinal ones. Activity of inflammatory bowel disease influenced the cytokine expression in gingival tissue. Copyright © 2017 Elsevier Ltd. All rights reserved.

The need to advance nutrition education in the training of health care professionals and recommended research to evaluate implementation and effectiveness1234

PubMed Central

Kris-Etherton, Penny M; Akabas, Sharon R; Bales, Connie W; Bistrian, Bruce; Braun, Lynne; Edwards, Marilyn S; Laur, Celia; Lenders, Carine M; Levy, Matthew D; Palmer, Carole A; Pratt, Charlotte A; Ray, Sumantra; Rock, Cheryl L; Saltzman, Edward; Seidner, Douglas L; Van Horn, Linda

2014-01-01

Nutrition is a recognized determinant in 3 (ie, diseases of the heart, malignant neoplasms, cerebrovascular diseases) of the top 4 leading causes of death in the United States. However, many health care providers are not adequately trained to address lifestyle recommendations that include nutrition and physical activity behaviors in a manner that could mitigate disease development or progression. This contributes to a compelling need to markedly improve nutrition education for health care professionals and to establish curricular standards and requisite nutrition and physical activity competencies in the education, training, and continuing education for health care professionals. This article reports the present status of nutrition and physical activity education for health care professionals, evaluates the current pedagogic models, and underscores the urgent need to realign and synergize these models to reflect evidence-based and outcomes-focused education. PMID:24717343

Pathogenesis of the limb manifestations and exercise limitations in peripheral artery disease.

PubMed

Hiatt, William R; Armstrong, Ehrin J; Larson, Christopher J; Brass, Eric P

2015-04-24

Patients with peripheral artery disease have a marked reduction in exercise performance and daily ambulatory activity irrespective of their limb symptoms of classic or atypical claudication. This review will evaluate the multiple pathophysiologic mechanisms underlying the exercise impairment in peripheral artery disease based on an evaluation of the current literature and research performed by the authors. Peripheral artery disease results in atherosclerotic obstructions in the major conduit arteries supplying the lower extremities. This arterial disease process impairs the supply of oxygen and metabolic substrates needed to match the metabolic demand generated by active skeletal muscle during walking exercise. However, the hemodynamic impairment associated with the occlusive disease process does not fully account for the reduced exercise impairment, indicating that additional pathophysiologic mechanisms contribute to the limb manifestations. These mechanisms include a cascade of pathophysiological responses during exercise-induced ischemia and reperfusion at rest that are associated with endothelial dysfunction, oxidant stress, inflammation, and muscle metabolic abnormalities that provide opportunities for targeted therapeutic interventions to address the complex pathophysiology of the exercise impairment in peripheral artery disease. © 2015 American Heart Association, Inc.

A framework for evaluating community-based physical activity promotion programmes in Latin America.

PubMed

Schmid, Thomas L; Librett, John; Neiman, Andrea; Pratt, Michael; Salmon, Art

2006-01-01

A growing interest in promoting physical activity through multi-sectoral community-based programmes has highlighted the need for effective programme evaluation. Meeting in Rio de Janeiro, an international workgroup of behavioural, medical, public health and other scientists and practitioners endorsed the principle of careful evaluation of all programmes and in a consensus process developed the Rio de Janeiro Recommendations for Evaluation of Physical Activity Interventions". Among these recommendations and principles were that when possible, evaluation should 'built into' the programme from the beginning. The workgroup also called for adequate funding for evaluation, setting a goal of about 10% of programme resources for evaluation. The group also determined that evaluations should be developed in conjunction with and the results shared with all appropriate stakeholders in the programme; evaluations should be guided by ethical standards such as those proposed by the American Evaluation Association and should assess programme processes as well as outcomes; evaluation outcomes should be used to revise and refine ongoing programmes and guide decisions about programme continuation or expansion. It was also recognised that additional training in programme evaluation is needed and the Centers for Disease Control and Prevention's Physical Activity Evaluation Handbook could be easily adapted for use in culturally diverse communities, especially in Latin America. This paper describes a 6-step evaluation process and provides the full set of recommendations from the Rio de Janeiro Workgroup. The handbook has been translated and additional case studies from Colombia and Brazil have been added. Spanish and Portuguese language editions of the Evaluation Handbook are available from the Centers for Disease Control and Prevention, Physical Activity and Health Branch.

Impact of active and stable psoriasis on health-related quality of life: the PSO-LIFE study.

PubMed

Daudén, E; Herrera, E; Puig, L; Sánchez-Carazo, J L; Toribio, J; Perulero, N

2013-10-01

The aim of this study was to assess the impact of psoriasis on health-related quality of life (HRQOL) using different questionnaires. Prospective observational study of patients with plaque psoriasis of at least 6 months' duration stratified by active and stable disease. The patients were evaluated at baseline, 7 days, and 12 weeks. At the 3 visits, the investigators recorded sociodemographic and clinical data and the patients completed the following HRQOL questionnaires: the Dermatology Life Quality Index (DLQI), the Psoriasis Disability Index (PDI), and psoriasis quality of life questionnaire (PSO-LIFE). In total, 304 patients (182 with active psoriasis and 122 with stable psoriasis) were evaluated. The mean (SD) age was 45.3 (14.5) years, and 56.3% of the group were men. At baseline, the mean (SD) psoriasis and area severity index (PASI) score was 17.0 (7.4) in patients with active disease and 5.6 (5.3) in those with stable disease; a reduction was seen in PASI scores during the evaluation period (P<.01). The mean (SD) score on the PSO-LIFE questionnaire increased significantly from 57.4 (20.4) to 72.2 (19.6) in patients with active psoriasis and from 76.4 (20.6) to 82.3 (18.3) in those with stable disease (P<0.01 in both groups). The difference in standardized mean scores between the 2 groups was 0.79 for the DLQI, 0.62 for the PDI, and 0.85 for the PSO-LIFE questionnaire. The impact of psoriasis on HRQOL as assessed by the PSO-LIFE questionnaire was greater in patients with lesions in visible areas than in those with less visible lesions (P<.01). Changes in PSO-LIFE and PASI scores were moderately and significantly correlated (r=-0.4). The impact of psoriasis on HRQOL is higher in patients with active disease. The PSO-LIFE questionnaire showed a greater tendency to discriminate between active and stable psoriasis than either the DLQI or the PDI. PSO-LIFE scores correlated significantly with lesion site and disease severity as measured by PASI. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

Fungicide seed treatments for evaluating the corn seedling disease complex following a winter rye cover crop

USDA-ARS?s Scientific Manuscript database

Seed treatments have been used to manage corn seedling diseases since the 1970’s and they contain a combination of active ingredients with specificity towards different pathogens. We hypothesized that using different seed treatment combinations and assessing seedling disease incidence and severity ...

Clinical composite measures of disease activity and damage used to evaluate patients with systemic lupus erythematosus: A systematic literature review.

PubMed

Castrejón, Isabel; Rúa-Figueroa, Iñigo; Rosario, María Piedad; Carmona, Loreto

2014-01-01

To determine the most appropriate indices to evaluate the disease activity and damage in patients with sytemic lupus erythematosus (SLE). A systematic literature search was performed to identify validation studies of indices used to evaluate disease activity and damage. We collected information for each instrument on every aspect of validation including feasibility, reliability, validity and sensitivity to change using ad hoc forms. A total of 38 articles were included addressing the validation of 6 composite indices to evaluate disease activity (BILAG, ECLAM, SLAM, SLEDAI, LAI and SLAQ); and 3 indices to evaluate damage (SLICC/ACE-DI, LDIQ and BILD). Only the SLAQ, LIDIQ and the BILD were self-administered. Feasibility and internal consistency was only studied in 3 indices (BILAG, SLAQ and SDI) with a Cronbach's α ranging from 0.35 to 0.87. The intra-observer reliability was examined by the intraclass correlation coefficient for BILAG with a result of 0.48 (95%CI: 0,23-0,81) and using analysis of variance for SLAM-R (0,78), SLEDAI (0,33) and the LAI (0,81). The inter-observer feasibility was evaluated using the correlation coefficient for ECLAM (0,90-0,93), the SLAM (0,86) and MEX-SLEDAI (0,97-0,89). The construct validity was examined by means of convergence with other instruments, specifically with global assessment by the physician, with similar results between indices (0,48-0,75). Lastly, responsiveness was tested in all indices except LAI, SDI and LDIQ, with a standardized response mean ranging from 0.12 to 0.75. Although multiple instruments have been validated for use in SLE it was not possible to find direct evidence of which is the most appropriate. BILAG and SLEDAI, with moderate feasibility and low responsiveness, are the 2 indices with a most complete validation and more extensively used. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Reliability, Validity, and Sensitivity to Change of Turkish Activities-Specific Balance Confidence Scale in Patients with Unilateral Peripheral Vestibular Disease

ERIC Educational Resources Information Center

Karapolat, Hale; Eyigor, Sibel; Kirazli, Yesim; Celebisoy, Nese; Bilgen, Cem; Kirazli, Tayfun

2010-01-01

The aim of this study is to evaluate the internal consistency, test-retest reliability, construct validity, and sensitivity to change of the Activities-specific Balance Confidence Scale (ABC) in people with peripheral vestibular disorder. Thirty-three patients with unilateral peripheral vestibular disease were included in the study. Patients were…

Clinical, biochemical, virological and sonographic profile of incidentally detected asymptomatic HBsAg positive subjects, in Bangladesh.

PubMed

Ishaque, S M; Mahmuduzzaman, M; Rahman, M A; Uddoula, M S; Rahman, M Z; Khan, M R; Chowdhury, M S

2014-01-01

Chronic hepatitis B virus (HBV) is known to be the significant cause of Liver related morbidity and mortality, affecting 400 million people worldwide and a major public health problem in Bangladesh where carrier rates of HBV infection varies from 7.5 to 10%. In Bangladesh prevalence of asymptomatic HBV infection and incidentally detected HBsAg positive subjects were not well studied. The aim of this study is to evaluate the disease activity, replicative status of the virus and to find out the stages of chronic liver disease among incidentally detected asymptomatic HBsAg positive Bangladeshi subjects. Two hundred (200) incidentally detected healthy HBsAg positive subject were evaluated clinically, biochemically, serologically and ultrasonographically from January 2004 to June 2008. HBeAg was found positive in 17(8.5%), anti-HBe was positive in 174(87%), raised serum ALT (>45iu/L) in 45(22.5%), prothrombine time (PT) >3 sec of control in 33(16.5%). Ultrasonography showed coarse hepatic echotexture in 13(6.5%). Evidence of active viral replication and signs of chronic liver disease were observed among incidentally detected healthy HBsAg positive subjects. Such individuals should be followed up at regular interval to evaluate the replicative status of the virus and disease activity so that appropriate measures could be initiated in time.

Antiviral activity of ovine interferon tau 4 against foot-and-mouth disease virus.

PubMed

Usharani, Jayaramaiah; Park, Sun Young; Cho, Eun-Ju; Kim, Chungsu; Ko, Young-Joon; Tark, Dongseob; Kim, Su-Mi; Park, Jong-Hyeon; Lee, Kwang-Nyeong; Lee, Myoung-Heon; Lee, Hyang-Sim

2017-07-01

Foot-and-mouth disease (FMD) is an economically important disease in most parts of the world and new therapeutic agents are needed to protect the animals before vaccination can trigger the host immune response. Although several interferons have been used for their antiviral activities against Foot-and-mouth disease virus (FMDV), ovine interferon tau 4 (OvIFN-τ4), with a broad-spectrum of action, cross-species antiviral activity, and lower incidence of toxicity in comparison to other type І interferons, has not yet been evaluated for this indication. This is the first study to evaluate the antiviral activity of OvIFN-τ4 against various strains of FMDV. The effective anti-cytopathic concentration of OvIFN-τ4 and its effectiveness pre- and post-infection with FMDV were tested in vitro in LFBK cells. In vivo activity of OvIFN-τ4 was then confirmed in a mouse model of infection. OvIFN-τ4 at a concentration of 500 ng, protected mice until 5days post-FMDV challenge and provided 90% protection for 10 days following FMDV challenge. These results suggest that OvIFN-τ4 could be used as an alternative to other interferons or antiviral agents at the time of FMD outbreak. Copyright © 2017. Published by Elsevier B.V.

Evaluation of a novel Serious Game based assessment tool for patients with Alzheimer's disease.

PubMed

Vallejo, Vanessa; Wyss, Patric; Rampa, Luca; Mitache, Andrei V; Müri, René M; Mosimann, Urs P; Nef, Tobias

2017-01-01

Despite growing interest in developing ecological assessment of difficulties in patients with Alzheimer's disease new methods assessing the cognitive difficulties related to functional activities are missing. To complete current evaluation, the use of Serious Games can be a promising approach as it offers the possibility to recreate a virtual environment with daily living activities and a precise and complete cognitive evaluation. The aim of the present study was to evaluate the usability and the screening potential of a new ecological tool for assessment of cognitive functions in patients with Alzheimer's disease. Eighteen patients with Alzheimer's disease and twenty healthy controls participated to the study. They were asked to complete six daily living virtual tasks assessing several cognitive functions: three navigation tasks, one shopping task, one cooking task and one table preparation task following a one-day scenario. Usability of the game was evaluated through a questionnaire and through the analysis of the computer interactions for the two groups. Furthermore, the performances in terms of time to achieve the task and percentage of completion on the several tasks were recorded. Results indicate that both groups subjectively found the game user friendly and they were objectively able to play the game without computer interactions difficulties. Comparison of the performances between the two groups indicated a significant difference in terms of percentage of achievement of the several tasks and in terms of time they needed to achieve the several tasks. This study suggests that this new Serious Game based assessment tool is a user-friendly and ecological method to evaluate the cognitive abilities related to the difficulties patients can encounter in daily living activities and can be used as a screening tool as it allowed to distinguish Alzheimer's patient's performance from healthy controls.

Hematopoietic stem cell transplantation in Niemann-Pick disease type B monitored by chitotriosidase activity.

PubMed

Quarello, Paola; Spada, Marco; Porta, Francesco; Vassallo, Elena; Timeus, Fabio; Fagioli, Franca

2018-02-01

Here, we report a patient with Niemann-Pick disease type B, with early severe onset of disease and pulmonary involvement, treated with hematopoietic stem cell transplant (HSCT) from a bone marrow matched unrelated donor. We confirm that HSCT is feasible and potentially beneficial for patients with severe phenotype. Noteworthy, we discussed the potential usefulness of the activity of peripheral chitotriosidase for the longitudinal evaluation of HSCT success and effectiveness. © 2017 Wiley Periodicals, Inc.

Evaluating Intra-Articular Drug Delivery for the Treatment of Osteoarthritis in a Rat Model

PubMed Central

Allen, Kyle D.; Adams, Samuel B.

2010-01-01

Osteoarthritis (OA) is a degenerative joint disease that can result in joint pain, loss of joint function, and deleterious effects on activity levels and lifestyle habits. Current therapies for OA are largely aimed at symptomatic relief and may have limited effects on the underlying cascade of joint degradation. Local drug delivery strategies may provide for the development of more successful OA treatment outcomes that have potential to reduce local joint inflammation, reduce joint destruction, offer pain relief, and restore patient activity levels and joint function. As increasing interest turns toward intra-articular drug delivery routes, parallel interest has emerged in evaluating drug biodistribution, safety, and efficacy in preclinical models. Rodent models provide major advantages for the development of drug delivery strategies, chiefly because of lower cost, successful replication of human OA-like characteristics, rapid disease development, and small joint volumes that enable use of lower total drug amounts during protocol development. These models, however, also offer the potential to investigate the therapeutic effects of local drug therapy on animal behavior, including pain sensitivity thresholds and locomotion characteristics. Herein, we describe a translational paradigm for the evaluation of an intra-articular drug delivery strategy in a rat OA model. This model, a rat interleukin-1β overexpression model, offers the ability to evaluate anti-interleukin-1 therapeutics for drug biodistribution, activity, and safety as well as the therapeutic relief of disease symptoms. Once the action against interleukin-1 is confirmed in vivo, the newly developed anti-inflammatory drug can be evaluated for evidence of disease-modifying effects in more complex preclinical models. PMID:19943805

Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer's disease cases.

PubMed

Taoka, Toshiaki; Masutani, Yoshitaka; Kawai, Hisashi; Nakane, Toshiki; Matsuoka, Kiwamu; Yasuno, Fumihiko; Kishimoto, Toshifumi; Naganawa, Shinji

2017-04-01

The activity of the glymphatic system is impaired in animal models of Alzheimer's disease (AD). We evaluated the activity of the human glymphatic system in cases of AD with a diffusion-based technique called diffusion tensor image analysis along the perivascular space (DTI-ALPS). Diffusion tensor images were acquired to calculate diffusivities in the x, y, and z axes of the plane of the lateral ventricle body in 31 patients. We evaluated the diffusivity along the perivascular spaces as well as projection fibers and association fibers separately, to acquire an index for diffusivity along the perivascular space (ALPS-index) and correlated them with the mini mental state examinations (MMSE) score. We found a significant negative correlation between diffusivity along the projection fibers and association fibers. We also observed a significant positive correlation between diffusivity along perivascular spaces shown as ALPS-index and the MMSE score, indicating lower water diffusivity along the perivascular space in relation to AD severity. Activity of the glymphatic system may be evaluated with diffusion images. Lower diffusivity along the perivascular space on DTI-APLS seems to reflect impairment of the glymphatic system. This method may be useful for evaluating the activity of the glymphatic system.

Antibodies against C1q Are a Valuable Serological Marker for Identification of Systemic Lupus Erythematosus Patients with Active Lupus Nephritis

PubMed Central

Chi, Shuhong; Yu, Yunxia; Shi, Juan; Zhang, Yurong; Yang, Jijuan; Yang, Lijuan; Liu, Xiaoming

2015-01-01

Objective. An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the diagnostic values of circulating autoantibodies to C1q alone or in combination with other markers for accessing active SLE and LN were evaluated. Methods. The diagnostic value of anti-C1q autoantibodies for identification of patients with active SLE disease and LN was evaluated by analyzing the level of anti-C1q antibodies in sera from 95 SLE patients, 40 non-SLE patients, and 34 healthy cohorts. Results. The prevalence of anti-C1q antibodies was significantly higher in patients with SLE (50/95, 52.6%), active SLE (40/51, 78.4%), and LN (30/35, 85.7%) in comparison with non-SLE patient controls, patients with inactive SLE, and non-LN, respectively. A combination of anti-C1q with anti-dsDNA and/or levels of complements C3 and C4 exhibited an increased specificity but a decreased sensitivity for identification of patients with active SLE and LN diseases relative to each of these markers alone. Conclusion. Anti-C1q antibodies were strongly associated with disease activity and LN in SLE patients, suggesting that it may be a reliable serological marker for identification of SLE patients with active LN and active SLE disease. PMID:26549923

Paediatric Crohn Disease: Disease Activity and Growth in the BELCRO Cohort After 3 Years Follow-up.

PubMed

De Greef, Elisabeth; Hoffman, Ilse; Smets, Francoise; Van Biervliet, Stephanie; Bontems, Patrick; Hauser, Bruno; Paquot, Isabelle; Alliet, Philippe; Arts, Wim; Dewit, Olivier; De Vos, Martine; Baert, Filip; Bossuyt, Peter; Rahier, Jean-Francois; Franchimont, Denis; Vermeire, Severine; Fontaine, Fernand; Louis, Edouard; Coche, J C; Veereman, Gigi

2016-08-01

The Belgian registry for paediatric Crohn disease (BELCRO) cohort is a prospective, multicentre registry for newly diagnosed paediatric patients with Crohn disease (CD) (<18 years) recruited from 2008 to 2010 to identify predictive factors for disease activity and growth. Data from the BELCRO database were evaluated at diagnosis, 24 and 36 months follow-up. At month 36 (M36), data were available on 84 of the 98 patients included at diagnosis. Disease activity evolved as follows: inactive 5% to 70%, mild 19% to 24%, and moderate to severe 76% to 6%. None of the variables such as age, sex, diagnostic delay, type of treatment, disease location, disease activity at diagnosis, and growth were associated with disease activity at M36. Paediatricians studied significantly less patients with active disease at M36 compared with adult physicians. Sixty percent of the patients had biologicals as part of their treatment at M36. Adult gastroenterologists initiated biologicals significantly earlier. They were the only factor determining biologicals' initiation, not disease location or disease severity at diagnosis. Median body mass index (BMI) z score evolved from -0.97 (range -5.5-2.1) to 0.11 (range -3.4-2) and median height z score from -0.15 (range -3.4-1.6) to 0.12 (range -2.3-2.3) at M36. None of the variables mentioned above influenced growth over time. Present treatment strategies lead to good disease control in the BELCRO cohort after 3 years. Logistic regression analysis did not show any influence of disease location or present treatment strategy on disease activity and growth, but patients under paediatric care had significantly less severe disease at M36.

Gastric and duodenal antiulcer activity of alkaloids: a review.

PubMed

de Sousa Falcão, Heloina; Leite, Jacqueline Alves; Barbosa-Filho, José Maria; de Athayde-Filho, Petrônio Filgueiras; de Oliveira Chaves, Maria Célia; Moura, Marcelo Dantas; Ferreira, Anderson Luiz; de Almeida, Ana Beatriz Albino; Souza-Brito, Alba Regina Monteiro; de Fátima Formiga Melo Diniz, Margareth; Batista, Leônia Maria

2008-12-17

Peptic ulcer disease is a deep gastrointestinal erosion disorder that involves the entire mucosal thickness and can even penetrate the muscular mucosa. Numerous natural products have been evaluated as therapeutics for the treatment of a variety of diseases, including this one. These products usually derive from plant and animal sources that contain active constituents such as alkaloids, flavonoids, terpenoids, tannins and others. The alkaloids are natural nitrogen-containing secondary metabolites mostly derived from amino acids and found in about 20% of plants. There has been considerable pharmacological research into the antiulcer activity of these compounds. In this work we review the literature on alkaloids with antiulcer activity, which covers about sixty-one alkaloids, fifty-five of which have activity against this disease when induced in animals.

Norrie disease gene is distinct from the monoamine oxidase genes.

PubMed

Sims, K B; Ozelius, L; Corey, T; Rinehart, W B; Liberfarb, R; Haines, J; Chen, W J; Norio, R; Sankila, E; de la Chapelle, A

1989-09-01

The genes for MAO-A and MAO-B appear to be very close to the Norrie disease gene, on the basis of loss and/or disruption of the MAO genes and activities in atypical Norrie disease patients deleted for the DXS7 locus; linkage among the MAO genes, the Norrie disease gene, and the DXS7 locus; and mapping of all these loci to the chromosomal region Xp11. The present study provides evidence that the MAO genes are not disrupted in "classic" Norrie disease patients. Genomic DNA from these "nondeletion" Norrie disease patients did not show rearrangements at the MAOA or DXS7 loci. Normal levels of MAO-A activities, as well as normal amounts and size of the MAO-A mRNA, were observed in cultured skin fibroblasts from these patients, and MAO-B activity in their platelets was normal. Catecholamine metabolites evaluated in plasma and urine were in the control range. Thus, although some atypical Norrie disease patients lack both MAO-A and MAO-B activities, MAO does not appear to be an etiologic factor in classic Norrie disease.

Activities of daily living and manual hand dexterity in persons with idiopathic parkinson disease.

PubMed

Choi, Yoo-Im; Song, Chiang-Soon; Chun, Byung-Yoon

2017-03-01

[Purpose] The purpose of this study was to evaluate the relationship between daily activities and manual dexterity in persons with Parkinson disease. [Subjects and Methods] The study participants were 25 patients with idiopathic Parkinson disease. This study used two clinical tools, the box-and-block test and Schwab and England Activities of Daily Living scale, to investigate the relationship between manual dexterity and Schwab and England Activities of Daily Living score. [Results] A positive correlation was observed between the Schwab and England Activities of Daily Living and the box-and-block test scores on the more and less affected sides. Moreover, the Schwab and England Activities of Daily Living score had a greater correlation with the box-and-block test score on the less affected side than that on the more affected side. [Conclusion] Manual dexterity and activities of daily living showed a positive correlation in individuals with Parkinson disease. The results of this study suggest that manual dexterity is an important factor for predicting physical performance in daily living in persons with Parkinson disease.

Positive association between leptin serum levels and disease activity on endoscopy in inflammatory bowel disease: A case-control study

PubMed Central

Trejo-Vazquez, Fabiola; Garza-Veloz, Idalia; Villela-Ramirez, Gabriela Alejandra; Ortiz-Castro, Yolanda; Mauricio-Saucedo, Panfilo; Cardenas-Vargas, Edith; Diaz-Baez, Mariana; Cid-Baez, Miguel A.; Castañeda-Miranda, Rodrigo; Ortiz-Rodriguez, Jose Manuel; Solis-Sanchez, Luis Octavio; Martinez-Fierro, Margarita L.

2018-01-01

Inflammatory bowel disease (IBD) includes ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis. As these subtypes of IBD display important differences in the behavior of the natural course of the disease, the identification of non-invasive markers for IBD is important. The aim of the present study was to evaluate the serum levels of 10 adipokines and their association with endoscopic activity in IBD. The 10-protein profile (C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, insulin, leptin, plasminogen activator inhibitor-1, resistin and visfatin) was evaluated using serum from 53 participants (23 UC and 11 CD patients, as well as 19 controls) from Zacatecas (Mexico) by using the Bio-Plex Pro Human Diabetes 10-Plex Panel (Bio-Rad Laboratories, Inc.). Compared with those in the controls, leptin levels were significantly lower in patients with IBD (P=4.9×10−4). In addition, serum leptin displayed differences between groups with and without disease activity on endoscopy (P<0.001). Among the study population, serum leptin levels of <5,494 pg/ml significantly increased the odds of IBD by 12.8-fold [odds ratio (OR)=12.8, 95% confidence interval (CI)=3.04–53.9, P=0.001]. In addition, patients with serum leptin levels of <2,498 pg/ml displayed 5.8-fold greater odds of disease activity on endoscopy among the study population (OR=5.8, 95% CI=1.52–22.4, P=0.013). No differences in the serum levels of the remaining proteins were identified between the groups. Among the study population, serum leptin was associated with an increased risk of IBD and with disease activity on endoscopy. Additional studies will be necessary to validate the use of leptin as a non-invasive biomarker of IBD severity. PMID:29545852

Cardiovascular evaluation of middle-aged/ senior individuals engaged in leisure-time sport activities: position stand from the sections of exercise physiology and sports cardiology of the European Association of Cardiovascular Prevention and Rehabilitation.

PubMed

Borjesson, Mats; Urhausen, Alex; Kouidi, Evangelia; Dugmore, Dorian; Sharma, Sanjay; Halle, Martin; Heidbüchel, Hein; Björnstad, Hans Halvor; Gielen, Stephan; Mezzani, Alessandro; Corrado, Domenico; Pelliccia, Antonio; Vanhees, Luc

2011-06-01

Regular aerobic exercise at moderate intensities and an increased physical fitness are associated with a reduced risk of fatal and nonfatal coronary events in middle-aged individuals. In contrast, moderate and vigorous physical exertion is associated with an increased risk for cardiac events, including sudden cardiac death in individuals harbouring cardiovascular disease. The risk-benefit ratio may differ in relation to the individual’s age, fitness level, and presence of cardiovascular disease; sedentary individuals with underlying coronary artery disease are at greatest risk. The intention of the present position stand of the European Association of Cardiovascular Prevention and Rehabilitation is to encourage individuals to participate in regular physical activity and derive the benefits of physical exercise while minimizing the risk of cardiovascular adverse events. Therefore, the aim is to establish the most practical method of cardiovascular evaluation in middle-age/senior individuals, who are contemplating exercise or who are already engaged in nonprofessional competitive or recreational leisure sporting activity. These recommendations rely on existing scientific evidence, and in the absence of such, on expert consensus. The methodology of how middle-aged and older individuals should be evaluated appropriately before engaging in regular physical activity is both complex and controversial. On practical grounds the consensus panel recommend that such evaluation should vary according to the individual’s cardiac risk profile and the intended level of physical activity. Self assessment of the habitual physical activity level and of the risk factors, are recommended for screening of large populations. Individuals deemed to be at risk require further evaluation by a qualified physician. In senior/adult individuals with an increased risk for coronary events, maximal exercise testing (and possibly further evaluations) is advocated. Hopefully, the recommendations in this paper provide a practical solution for facilitating safe exercise prescription in senior/adults.

The impact of high intensity interval training on disease activity and patient disease perception in patients with psoriatic arthritis: A randomized controlled trial.

PubMed

Thomsen, Ruth S; Nilsen, Tom I L; Haugeberg, Glenn; Bye, Anja; Kavanaugh, Arthur; Hoff, Mari

2018-06-08

The aim of this study was to evaluate the impact of high intensity interval training (HIIT) on disease activity and patient disease perception in patients with psoriatic arthritis (PsA), and evaluating if a potential effect could be sustained for a longer period. We randomly assigned 67 PsA patients (43 women and 24 men) to an intervention group performing HIIT for 11 weeks or a control group who were instructed to not change their physical exercise habits. Outcomes were assessed at three and nine months with the patient global assessment (PGA), fatigue, and pain measured on a 100 mm visual analog scale and the composite disease activity score of 44 joints (DAS44) was calculated. We used linear mixed models to calculate mean difference with 95% confidence interval (CI) between the groups according to the intention-to-treat principle. At three months there was no clear difference in PGA (-0.49; 95% CI -10.91 to 9.94), DAS44 (-0.08; 95% CI -0.36 to 0.20) or pain intensity (5.45; 95% CI -4.36 to 15.26) between the groups. However, the HIIT group reported less fatigue (-12.83; 95% CI -25.88 to 0.23) than the control group. There was no evidence of long-term effects of HIIT on outcomes measured at nine months. HIIT showed no clear effects on disease activity markers in patients with PsA, but the exercise group reported meaningfully less fatigue after the intervention period. This study suggests that PsA patients tolerate HIIT without deterioration of disease activity and with improvement in fatigue. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Thromboelastographic Evaluation of Dogs with Acute Liver Disease.

PubMed

Kelley, D; Lester, C; Shaw, S; de Laforcade, A; Webster, C R L

2015-01-01

Given the liver's pivotal role in hemostasis and fibrinolysis, the coagulopathy accompanying hepatic disease is complex. To prospectively evaluate kaolin-activated thromboelastography (TEG) in dogs with acute liver disease (ALD) and compare with plasma-based coagulation tests. Twenty-one dogs with a diagnosis of ALD based on recent onset of clinical signs accompanied by increases in serum bilirubin concentration and alanine aminotransferase activity. Clinical presentation, CBC, serum biochemistry, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and TEG analysis were evaluated in 21 dogs with a subset also having fibrinogen, antithrombin (AT) activity, protein C (PC) activity, d-dimers, and von Willebrand's factor (vWF) activity analyzed. A PT >1.5 times the upper limit of normal defined acute liver failure (ALF). Dogs with ALD had mean increases in R, K, LY30, PT, aPTT, and vWF activity, and decreases in angle, maximal amplitude (MA), G, AT activity, and PC activity. The TEG results defined dogs as hypocoagulable (11/21), normocoagulable (8/21), or hypercoagulable (2/21). Increases in LY30 defined 8/21 dogs as hyperfibrinolytic. Hypocoagulable and hyperfibrinolytic dogs had lower fibrinogen and PC activity than dogs without these abnormalities. Overall, ALF dogs had greater increases in K and LY30, and decreases in MA, G, and PC activity than dogs with less severe hepatic impairment. Results for MA and LY30 were positively correlated with serum bilirubin concentration and white blood cell count, and negatively correlated with serum cholesterol concentration. ALD dogs have a range of coagulation abnormalities that trend toward hypocoagulability and hyperfibrinolysis as functional impairment occurs. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Efficacy and safety at 24 weeks of daily clinical use of tofacitinib in patients with rheumatoid arthritis.

PubMed

Iwamoto, Naoki; Tsuji, Sosuke; Takatani, Ayuko; Shimizu, Toshimasa; Fukui, Shoichi; Umeda, Masataka; Nishino, Ayako; Horai, Yoshiro; Koga, Tomohiro; Kawashiri, Shin-Ya; Aramaki, Toshiyuki; Ichinose, Kunihiro; Hirai, Yasuko; Tamai, Mami; Nakamura, Hideki; Terada, Kaoru; Origuchi, Tomoki; Eguchi, Katsumi; Ueki, Yukitaka; Kawakami, Atsushi

2017-01-01

We evaluated the efficacy and safety of tofacitinib in patients with rheumatoid arthritis (RA) in a real-world setting. Seventy consecutive patients, for whom tofacitinib was initiated between November 2013 and May 2016, were enrolled. All patients fulfilled the 2010 ACR/EULAR classification criteria for RA. All patients received 5 mg of tofacitinib twice daily and were followed for 24 weeks. Clinical disease activity indicated by disease activity score (DAS)28-ESR, the simplified disease activity index, and the clinical disease activity index as well as adverse events (AEs) were evaluated. Statistical analysis was performed to determine which baseline variables influenced the efficacy of tofacitinib at 24 weeks. Fifty-eight patients (82.9%) continued tofacitinib at 24 weeks. Clinical disease activity rapidly and significantly decreased, and this efficacy continued throughout the 24 weeks: i.e., DAS28-ESR decreased from 5.04 ± 1.33 at baseline to 3.83 ± 1.11 at 4 weeks and 3.53 ± 1.17 at 24 weeks (P<0.0001, vs. baseline). 15 AEs including 5 herpes zoster infection occurred during tofacitinib treatment. The efficacy of tofacitinib was not changed in patients without concomitant use of methotrexate (MTX) or patients whose treatment with tocilizumab (TCZ) failed. Multivariable logistic analysis showed that the number of biologic DMARDs (bDMARDs) previously used was independently associated with achievement of DAS-low disease activity. Our present study suggests that tofacitinib is effective in real-world settings even without concomitant MTX use or after switching from TCZ. Our results also suggest that its efficacy diminishes if started after use of multiple bDMARDs.

Efficacy and safety at 24 weeks of daily clinical use of tofacitinib in patients with rheumatoid arthritis

PubMed Central

Tsuji, Sosuke; Takatani, Ayuko; Shimizu, Toshimasa; Fukui, Shoichi; Umeda, Masataka; Nishino, Ayako; Horai, Yoshiro; Koga, Tomohiro; Kawashiri, Shin-ya; Aramaki, Toshiyuki; Ichinose, Kunihiro; Hirai, Yasuko; Tamai, Mami; Nakamura, Hideki; Terada, Kaoru; Origuchi, Tomoki; Eguchi, Katsumi; Ueki, Yukitaka; Kawakami, Atsushi

2017-01-01

Objective We evaluated the efficacy and safety of tofacitinib in patients with rheumatoid arthritis (RA) in a real-world setting. Methods Seventy consecutive patients, for whom tofacitinib was initiated between November 2013 and May 2016, were enrolled. All patients fulfilled the 2010 ACR/EULAR classification criteria for RA. All patients received 5 mg of tofacitinib twice daily and were followed for 24 weeks. Clinical disease activity indicated by disease activity score (DAS)28-ESR, the simplified disease activity index, and the clinical disease activity index as well as adverse events (AEs) were evaluated. Statistical analysis was performed to determine which baseline variables influenced the efficacy of tofacitinib at 24 weeks. Results Fifty-eight patients (82.9%) continued tofacitinib at 24 weeks. Clinical disease activity rapidly and significantly decreased, and this efficacy continued throughout the 24 weeks: i.e., DAS28-ESR decreased from 5.04 ± 1.33 at baseline to 3.83 ± 1.11 at 4 weeks and 3.53 ± 1.17 at 24 weeks (P<0.0001, vs. baseline). 15 AEs including 5 herpes zoster infection occurred during tofacitinib treatment. The efficacy of tofacitinib was not changed in patients without concomitant use of methotrexate (MTX) or patients whose treatment with tocilizumab (TCZ) failed. Multivariable logistic analysis showed that the number of biologic DMARDs (bDMARDs) previously used was independently associated with achievement of DAS-low disease activity. Conclusions Our present study suggests that tofacitinib is effective in real-world settings even without concomitant MTX use or after switching from TCZ. Our results also suggest that its efficacy diminishes if started after use of multiple bDMARDs. PMID:28472115

Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

PubMed

Martin, Naomi H; Ibrahim, Fowzia; Tom, Brian; Galloway, James; Wailoo, Allan; Tosh, Jonathan; Lempp, Heidi; Prothero, Louise; Georgopoulou, Sofia; Sturt, Jackie; Scott, David L

2017-12-08

Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen in patients with established rheumatoid arthritis who have moderately active disease. It will evaluate both the clinical and cost-effectiveness of intensive treatment. Current Controlled Trials, ID: ISRCTN70160382 . Registered on 16 January 2014.

Improved clinical, functional and work outcomes in spondyloarthritides during real-life adalimumab treatment in central-eastern Europe.

PubMed

Szántó, Sándor; Poór, Gyula; Opris, Daniela; Iaremenko, Oleg; Procházková, Leona; Kuuse, Reet; Nagy, Orsolya; Chernyshov, Valentyn; Géher, Pál

2016-08-01

Adalimumab effectiveness on clinical, functional and work-related outcomes was evaluated in patients with active ankylosing spondylitis or psoriatic arthritis treated in routine clinical practice in central-eastern Europe. Patients (n = 555) were followed for 12 months. Primary end point was percentage of patients with a treatment response (≥50% decrease from baseline in Bath Ankylosing Spondylitis Disease Activity Index or ≥1.2 point decrease from baseline in Disease Activity Index-28 joint for axial or peripheral symptoms, respectively). Functional status was evaluated by the Bath Ankylosing Spondylitis Functional Index and Health Assessment Questionnaire Disability Index. Working ability was evaluated by the Work Productivity and Activity Impairment Questionnaire - Specific Health Problem. 76.1% of patients with axial symptoms and 83.5% with peripheral symptoms achieved a treatment response. Frequency of extra-articular manifestations decreased. Improvements were observed in functional status and workability. No new safety signals were observed. Adalimumab was effective and well tolerated during real-world use in central-eastern Europe.

Effector T-cells are expanded in systemic lupus erythematosus patients with high disease activity and damage indexes.

PubMed

Piantoni, S; Regola, F; Zanola, A; Andreoli, L; Dall'Ara, F; Tincani, A; Airo', P

2018-01-01

Background and objectives T-cell activation may be one of the pathogenic mechanisms of systemic lupus erythematosus (SLE). After repeated antigenic stimulation, T-cells undergo different modifications, leading to the differentiation into effector memory T-cells (CCR7-CD45RA-) and terminally differentiated effector memory (TDEM) T-cells (CCR7-CD45RA+). Similarly, down-modulation of CD28 may lead to the expansion of the CD28- T-cells, a subpopulation with peculiar effector activities. The aim of this study was the characterization of T-cell phenotype in a cohort of patients with SLE according to disease activity and damage index. Materials and methods Phenotypic analysis of peripheral blood T lymphocytes of 51 SLE patients and 21 healthy controls was done by flow-cytometry. SLE disease activity was evaluated by SLE Disease Activity Index-2000 (SLEDAI-2K) and damage by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). The variations between different groups were evaluated by Mann-Whitney test. Bonferroni correction was applied to adjust for multiple comparisons ( p adj ). Spearman rank test was used to evaluate the correlations between quantitative variables. Results CD4+ lymphopenia was found among SLE patients. Patients showed a trend for a higher percentage of TDEM among the CD4+ T-cell subpopulation in comparison with healthy controls ( p = .04). SLE patients were divided into two groups according to disease activity: patients with SLEDAI-2K ≥ 6 ( n = 13) had a higher percentage of circulating CD4+ T-cells with CD28- phenotype ( p adj  = .005) as well as those with an effector memory ( p adj  = .004) and TDEM ( p adj  = .002) phenotype and a trend of decrease of regulatory T-cells (TREGs) ( p = .02), in comparison with patients with low disease activity ( n = 38). Patients with damage (SDI ≥ 1) tended to show an expansion of TDEM among CD4+ T-cells as compared with patients with no damage ( p = .01). In SLE patients an inverse correlation was found between the percentages of TREGs and those of TDEM ( p < .01) or CD4 + CD28- ( p < .01) T-cells. Conclusions CD4+ T-cell subpopulations displaying phenotype characteristics of effector lymphocytes are proportionally expanded in patients with active SLE and a higher damage index. These findings may suggest a role of effector T-cells in the pathogenesis of the disease and in the mechanisms of damage in SLE.

Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases

PubMed Central

Lin, Gu-Jiun; Huang, Shing-Hwa; Chen, Shyi-Jou; Wang, Chih-Hung; Chang, Deh-Ming; Sytwu, Huey-Kang

2013-01-01

Melatonin is the major secretory product of the pineal gland during the night and has multiple activities including the regulation of circadian and seasonal rhythms, and antioxidant and anti-inflammatory effects. It also possesses the ability to modulate immune responses by regulation of the T helper 1/2 balance and cytokine production. Autoimmune diseases, which result from the activation of immune cells by autoantigens released from normal tissues, affect around 5% of the population. Activation of autoantigen-specific immune cells leads to subsequent damage of target tissues by these activated cells. Melatonin therapy has been investigated in several animal models of autoimmune disease, where it has a beneficial effect in a number of models excepting rheumatoid arthritis, and has been evaluated in clinical autoimmune diseases including rheumatoid arthritis and ulcerative colitis. This review summarizes and highlights the role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus, and inflammatory bowel disease. PMID:23727938

Antiplatelet drugs reduce the immunoinflammatory response in a rat model of periodontal disease.

PubMed

Coimbra, L S; Steffens, J P; Muscará, M N; Rossa, C; Spolidorio, L C

2014-12-01

After activation, platelets express mediators that modulate inflammation. We hypothesized that drug-induced platelet inactivation may interfere in the inflammatory process in experimental periodontal disease by suppressing the release of biological mediators to the injury site. To evaluate the effects of antiplatelet drugs on experimental periodontal disease, 60 rats were randomly assigned to six groups (n = 10) and ligatures were placed around lower first molars in three groups. The other three groups were not subjected to the induction of periodontal disease and were used as negative controls. During the experimental period, animals were given aspirin (30 mg/kg) or clopidogrel (75 mg/kg) intragastrically once daily for 3 d. On day 3, they were killed and gingival tissue were used to evaluate myeloperoxidase activity and the expression of the chemokine CXCL4. Hemi-mandibles were used for microscopic evaluation. Clopidogrel significantly reduced the inflammatory infiltrate and increased the amount of collagen fibers. Histometric analysis showed that clopidogrel impaired alveolar bone loss. Expression of CXCL4 was significantly increased (p < 0.001) in rats subjected to periodontal disease. Systemic administration of aspirin and clopidogrel induced a significant decrease ( p < 0.05) in the expression of CXCL4. Treatment with antiplatelet drugs resulted in a significant reduction of myeloperoxidase activity when compared to saline-treated animals with periodontal disease. Clopidogrel but not aspirin showed the ability of preventing bone loss in experimental periodontitis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of athletes with complex congenital heart disease.

PubMed

Bates, Benjamin A; Richards, Camille; Hall, Michael; Kerut, Edmund K; Campbell, William; McMullan, Michael R

2017-06-01

As a result of improvements in congenital heart surgery, there are more adults alive today with congenital heart disease (CHD) than children. Individuals with cardiac birth defects may be able to participate in physical activities but require proper cardiovascular evaluation. The American Heart Association and American College of Cardiology released guidelines in 2015 for athletes with cardiovascular abnormalities. The guidelines express that although restriction from competitive athletics may be indicated for some, the majority of individuals with CHD can and should engage in some form of physical activity. This case study demonstrates the importance of combining all aspects of history, physical examination, ECG, and imaging modalities to evaluate cardiac anatomy and function in young athletes with complex CHD. © 2017, Wiley Periodicals, Inc.

Youth participatory research and evaluation to inform a Chagas disease prevention program in Ecuador.

PubMed

Marco-Crespo, Belén; Casapulla, Sharon; Nieto-Sanchez, Claudia; Urrego, J Guillermo Gómez; Grijalva, Mario J

2018-04-30

This qualitative study engaged a group of young people in participatory research and evaluation activities in order to study to what extent engaging youth in health interventions can inform research and evaluation processes. We applied a youth participatory research and evaluation approach (PRE) to inform research and evaluation on the impact of a Chagas disease control program in southern Ecuador. Our main interest was to examine the methodological contributions of PRE to knowledge sharing for health intervention planning in the context of global health and neglected tropical diseases. The results of this study suggest that by demystifying research and evaluation practices and rendering them accessible and relevant, marginalized youth can develop critical and reflexive thinking skills that could be useful for decision-making on health promotion. Our findings also reveal the potential of youth as active participants in project development in ways that enhance, validate, and improve health interventions. Young people are interested in learning about and sharing local knowledge that can benefit research and evaluation processes. Despite the numerous strengths demonstrated by PRE, the inherent complexities of international development, such as cultural differences, asymmetrical power relations, and the ongoing challenges of sustainability, remain. Copyright © 2018 Elsevier Ltd. All rights reserved.

Development of a Multi-Biomarker Disease Activity Test for Rheumatoid Arthritis

PubMed Central

Shen, Yijing; Ramanujan, Saroja; Knowlton, Nicholas; Swan, Kathryn A.; Turner, Mary; Sutton, Chris; Smith, Dustin R.; Haney, Douglas J.; Chernoff, David; Hesterberg, Lyndal K.; Carulli, John P.; Taylor, Peter C.; Shadick, Nancy A.; Weinblatt, Michael E.; Curtis, Jeffrey R.

2013-01-01

Background Disease activity measurement is a key component of rheumatoid arthritis (RA) management. Biomarkers that capture the complex and heterogeneous biology of RA have the potential to complement clinical disease activity assessment. Objectives To develop a multi-biomarker disease activity (MBDA) test for rheumatoid arthritis. Methods Candidate serum protein biomarkers were selected from extensive literature screens, bioinformatics databases, mRNA expression and protein microarray data. Quantitative assays were identified and optimized for measuring candidate biomarkers in RA patient sera. Biomarkers with qualifying assays were prioritized in a series of studies based on their correlations to RA clinical disease activity (e.g. the Disease Activity Score 28-C-Reactive Protein [DAS28-CRP], a validated metric commonly used in clinical trials) and their contributions to multivariate models. Prioritized biomarkers were used to train an algorithm to measure disease activity, assessed by correlation to DAS and area under the receiver operating characteristic curve for classification of low vs. moderate/high disease activity. The effect of comorbidities on the MBDA score was evaluated using linear models with adjustment for multiple hypothesis testing. Results 130 candidate biomarkers were tested in feasibility studies and 25 were selected for algorithm training. Multi-biomarker statistical models outperformed individual biomarkers at estimating disease activity. Biomarker-based scores were significantly correlated with DAS28-CRP and could discriminate patients with low vs. moderate/high clinical disease activity. Such scores were also able to track changes in DAS28-CRP and were significantly associated with both joint inflammation measured by ultrasound and damage progression measured by radiography. The final MBDA algorithm uses 12 biomarkers to generate an MBDA score between 1 and 100. No significant effects on the MBDA score were found for common comorbidities. Conclusion We followed a stepwise approach to develop a quantitative serum-based measure of RA disease activity, based on 12-biomarkers, which was consistently associated with clinical disease activity levels. PMID:23585841

Development of a multi-biomarker disease activity test for rheumatoid arthritis.

PubMed

Centola, Michael; Cavet, Guy; Shen, Yijing; Ramanujan, Saroja; Knowlton, Nicholas; Swan, Kathryn A; Turner, Mary; Sutton, Chris; Smith, Dustin R; Haney, Douglas J; Chernoff, David; Hesterberg, Lyndal K; Carulli, John P; Taylor, Peter C; Shadick, Nancy A; Weinblatt, Michael E; Curtis, Jeffrey R

2013-01-01

Disease activity measurement is a key component of rheumatoid arthritis (RA) management. Biomarkers that capture the complex and heterogeneous biology of RA have the potential to complement clinical disease activity assessment. To develop a multi-biomarker disease activity (MBDA) test for rheumatoid arthritis. Candidate serum protein biomarkers were selected from extensive literature screens, bioinformatics databases, mRNA expression and protein microarray data. Quantitative assays were identified and optimized for measuring candidate biomarkers in RA patient sera. Biomarkers with qualifying assays were prioritized in a series of studies based on their correlations to RA clinical disease activity (e.g. the Disease Activity Score 28-C-Reactive Protein [DAS28-CRP], a validated metric commonly used in clinical trials) and their contributions to multivariate models. Prioritized biomarkers were used to train an algorithm to measure disease activity, assessed by correlation to DAS and area under the receiver operating characteristic curve for classification of low vs. moderate/high disease activity. The effect of comorbidities on the MBDA score was evaluated using linear models with adjustment for multiple hypothesis testing. 130 candidate biomarkers were tested in feasibility studies and 25 were selected for algorithm training. Multi-biomarker statistical models outperformed individual biomarkers at estimating disease activity. Biomarker-based scores were significantly correlated with DAS28-CRP and could discriminate patients with low vs. moderate/high clinical disease activity. Such scores were also able to track changes in DAS28-CRP and were significantly associated with both joint inflammation measured by ultrasound and damage progression measured by radiography. The final MBDA algorithm uses 12 biomarkers to generate an MBDA score between 1 and 100. No significant effects on the MBDA score were found for common comorbidities. We followed a stepwise approach to develop a quantitative serum-based measure of RA disease activity, based on 12-biomarkers, which was consistently associated with clinical disease activity levels.

Vitamin D insufficiency and deficiency in mexican patients with systemic lupus erythematosus: Prevalence and relationship with disease activity.

PubMed

García-Carrasco, Mario; Mendoza-Pinto, Claudia; Etchegaray-Morales, Ivet; Soto-Santillán, Pamela; Jiménez-Herrera, Erick Alejandro; Robles-Sánchez, Viridiana; Rodríguez-Gallegos, Alma; Ramos-Varela, Araceli; Muñoz-Guarneros, Margarita; Ruiz-Argüelles, Alejandro

To determine and compare the prevalence of vitamin D insufficiency and deficiency in patients with systemic lupus erythematosus (SLE) with and without disease activity. We made a comparative, observational, cross-sectional, prospective study of 137 women with SLE according to American College of Rheumatology criteria. Patients with chronic kidney disease, cancer, hyperparathyroidism, pregnancy, and lactation were excluded. Disease activity was assessed using the MEX-SLEDAI score: a score of ≥3 was considered as disease activity. Data were collected on diabetes mellitus, the use of corticosteroids, chloroquine, and immunosuppressants, photoprotection and vitamin D supplementation. Vitamin D levels were measured by chemiluminescent immunoassay: insufficiency was defined as serum 25-hydroxyvitamin D <30ng/ml and deficiency as <10ng/ml. 137 women with SLE (mean age 45.9±11.6 years, disease duration 7.7±3.4 years) were evaluated. Mean disease activity was 2 (0-8): 106 patients had no disease activity and 31 had active disease (77.4% versus 22.6%). Vitamin D insufficiency and deficiency was found in 122(89.0%) and 4 (2.9%) patients, respectively. There was no significant difference in vitamin D levels between patients with and without active disease (19.3±4.5 versus 19.7±6.8; P=.75). No correlation between the MEX-SLEDAI score (P=.21), photosensitivity, photoprotection, prednisone or chloroquine use and vitamin D supplementation was found. Women with SLE had a high prevalence of vitamin D insufficient. No association between vitamin D levels and disease activity was found. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Brigatinib for the treatment of ALK-positive advanced non-small cell lung cancer patients.

PubMed

Passaro, A; Prelaj, A; Pochesci, A; Spitaleri, G; Rossi, G; Del Signore, E; Catania, C; de Marinis, F

2017-08-01

Brigatinib (AP-26113, Alunbrig) is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) that is highly active in non-small cell lung cancer (NSCLC) harboring ALK translocation. Brigatinib was found to be very active against different ALK resistance mutations that mediate acquired resistance biology processes, particularly G1269A ALK C1156Y, I1171S/T, V1180L and others. Different clinical trials evaluated the activity of brigatinib in crizotinib-resistant patients, confirming high activity with durable response not only in parenchymal disease, but also in intracranial disease. Nowadays, brigatinib is under evaluation in different clinical trials exploring TKI-naive patients in the first-line setting. On the basis of its significant activity results, brigatinib received approval by the FDA for the treatment of patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib. Copyright 2017 Clarivate Analytics.

Work productivity is associated with disease activity and functional ability in Italian patients with early axial spondyloarthritis: an observational study from the SPACE cohort.

PubMed

de Hooge, Manouk; Ramonda, Roberta; Lorenzin, Mariagrazia; Frallonardo, Paola; Punzi, Leonardo; Ortolan, Augusta; Doria, Andrea

2016-11-16

Spondyloarthritis often affects young people, typically in their working years. The aim of our study was to investigate work productivity and its relationship with disease activity and physical functioning in Italian patients with axial spondyloarthritis (axSpA) with chronic back pain (CBP) for ≥3 months and ≤2 years, and onset  < 45 years of age. Baseline absenteeism, presenteeism, work productivity loss (assessed by the Work Productivity and Activity Impairment questionnaire (WPAI)), and disease activity (assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)/Ankylosing Spondylitis Disease Activity Score (ASDAS)) and functional ability (assessed by the Bath Ankylosing Spondylitis Disease Functional Index (BASFI)) of patients with axSpA (rheumatologist's diagnosis) included in the Italian section of the Spondyloarthritis Caught Early (SPACE) cohort were collected. Multivariate linear regression analysis was used to evaluate the associations between work productivity and disease activity/physical functioning. Absenteeism in 51 patients with axSpA was low (8.3 %). A decrease in work productivity was related to an increase in disease activity. Disease activity was strongly correlated with absenteeism (p < 0.01), presenteeism (p < 0.01) and work productivity loss (p < 0.001). In addition, decreased work productivity was related to a decrease in functional ability. Physical functioning was correlated with absenteeism (p < 0.001), presenteeism (p < 0.05) and work productivity loss (p < 0.001). Impairment of work productivity was correlated with disease activity and physical functioning in Italian patients with axSpA with CBP for ≥3 months and ≤2 years, with onset <45 years of age.

Education, leisure activities and cognitive and functional ability of Alzheimer's disease patients: A follow-up study

PubMed Central

Sobral, Margarida; Paúl, Constança

2013-01-01

Education and participation in leisure activities appear to be highly relevant variables in Alzheimer's disease (AD) and usually form the basis of the Cognitive Reserve construct. OBJECTIVE [A] To determine the association between education, cognitive and functional ability of AD patients; [B] To determine the association between participation in leisure activities and cognitive and functional ability of AD patients; [C] To evaluate the association of education and participation in leisure activities in the course of AD. METHODS Functional and neuropsychological abilities of 120 outpatients with probable AD were evaluated at baseline, at 36 and 54 months. Data collected at baseline included socio-demographics, clinical variables, education and frequency of participation in leisure activities throughout life. All participants and/or caregivers answered the questionnaire, "Participation in leisure activities throughout life" while patients completed the MMSE, the Clinical Dementia Rating scale, neuropsychological tests from the Lisbon Screening for Dementia Assessment, Barthel Index and Lawton and Brody's Index. RESULTS AD patients with higher levels of education achieved better results on cognitive tests. The participants with higher participation in leisure activities exhibited better results on cognitive and functional tests than those with lower participation. The disease progression was linear and progressed similarly regardless of the level of education of participants. However, the results suggest a slower disease progression in patients with a higher level of participation in leisure activities throughout their lives. CONCLUSION AD patients with high education and high participation in leisure activities may benefit from a slower cognitive and functional decline after diagnosis of AD. PMID:29213838

Nutrition and Physical Activity Knowledge Assessment: Development of Questionnaires and Evaluation of Reliability in African American and Latino Children

ERIC Educational Resources Information Center

Roberts, Lindsay S.; Sharma, Sushma; Hudes, Mark L.; Fleming, Sharon E.

2012-01-01

Background: African-American and Latino children living in neighborhoods with a low-socioeconomic index are more at risk of obesity-associated metabolic disease than their higher socioeconomic index and/or white peers. Currently, consistent and reliable questionnaires to evaluate nutrition and physical activity knowledge in these children are…

Use of telemedicine technologies in the management of infectious diseases: a review.

PubMed

Parmar, Parmvir; Mackie, David; Varghese, Sunil; Cooper, Curtis

2015-04-01

Telemedicine technologies are rapidly being integrated into infectious diseases programs with the aim of increasing access to infectious diseases specialty care for isolated populations and reducing costs. We summarize the utility and effectiveness of telemedicine in the evaluation and treatment of infectious diseases patients. The use of telemedicine in the management of acute infectious diseases, chronic hepatitis C, human immunodeficiency virus, and active pulmonary tuberculosis is considered. We recapitulate and evaluate the advantages of telemedicine described in other studies, present challenges to adopting telemedicine, and identify future opportunities for the use of telemedicine within the realm of clinical infectious diseases. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Assessing Health Status in Inflammatory Bowel Disease using a Novel Single-Item Numeric Rating Scale

PubMed Central

Surti, Bijal; Spiegel, Brennan; Ippoliti, Andrew; Vasiliauskas, Eric; Simpson, Peter; Shih, David; Targan, Stephan; McGovern, Dermot; Melmed, Gil Y.

2014-01-01

Background Current instruments used to measure disease activity and health-related quality of life (HRQOL) in patients with Crohn’s disease (CD) and ulcerative colitis (UC) are often cumbersome, time-consuming, and expensive; although used in clinical trials, they are not convenient for clinical practice. A numeric rating scale (NRS) is a quick, inexpensive, and convenient patient-reported outcome (PRO) that can capture the patient’s overall perception of health. Aims To assess the validity, reliability, and responsiveness of an NRS and evaluate its use in clinical practice in patients with CD and UC. Methods We prospectively evaluated patient-reported NRS scores and measured correlations between NRS and a range of severity measures, including physician-reported NRS, Crohn’s disease activity index (CDAI), Harvey-Bradshaw index (HBI), inflammatory bowel disease questionnaire (IBDQ), and C-reactive protein (CRP) in patients with CD. Subsequently, we evaluated the correlation between the NRS and standard measures of health status (HBI or simple colitis clinical activity index [SCCAI]) and laboratory tests (sedimentation rate [ESR], CRP, and fecal calprotectin) in patients with CD and UC. Results The patient-reported NRS showed excellent correlation with CDAI (R2=0.59, p<0.0001), IBDQ (R2=0.66, p<0.0001), and HBI (R2=0.32, p<0.0001) in patients with CD. The NRS showed poor, but statistically significant correlation with SCCAI (R2=0.25, p<0.0001) in patients with UC. The NRS did not correlate with CRP, ESR, or calprotectin. The NRS was reliable and responsive to change. Conclusions The NRS is a valid, reliable, and responsive measure that may be useful to evaluate patients with CD and possibly UC. PMID:23250673

Assessing health status in inflammatory bowel disease using a novel single-item numeric rating scale.

PubMed

Surti, Bijal; Spiegel, Brennan; Ippoliti, Andrew; Vasiliauskas, Eric A; Simpson, Peter; Shih, David Q; Targan, Stephan R; McGovern, Dermot P B; Melmed, Gil Y

2013-05-01

Current instruments used to measure disease activity and health-related quality of life in patients with Crohn's disease (CD) and ulcerative colitis (UC) are often cumbersome, time-consuming, and expensive; although used in clinical trials, they are not convenient for clinical practice. A numeric rating scale (NRS) is a quick, inexpensive, and convenient patient-reported outcome that can capture the patient's overall perception of health. The aim of this study was to assess the validity, reliability, and responsiveness of an NRS and evaluate its use in clinical practice in patients with CD and UC. We prospectively evaluated patient-reported NRS scores and measured correlations between NRS and a range of severity measures, including physician-reported NRS, Crohn's disease activity index (CDAI), Harvey-Bradshaw index (HBI), inflammatory bowel disease questionnaire (IBDQ), and C-reactive protein (CRP) in patients with CD. Subsequently, we evaluated the correlation between the NRS and standard measures of health status (HBI or simple colitis clinical activity index [SCCAI]) and laboratory tests (sedimentation rate [ESR], CRP, and fecal calprotectin) in patients with CD and UC. The patient-reported NRS showed excellent correlation with CDAI (R (2) = 0.59, p < 0.0001), IBDQ (R (2) = 0.66, p < 0.0001), and HBI (R (2) = 0.32, p < 0.0001) in patients with CD. The NRS showed poor, but statistically significant correlation with SCCAI (R (2) = 0.25, p < 0.0001) in patients with UC. The NRS did not correlate with CRP, ESR, or calprotectin. The NRS was reliable and responsive to change. The NRS is a valid, reliable, and responsive measure that may be useful to evaluate patients with CD and possibly UC.

Signum, a new fungicide for control of leaf diseases in outdoor vegetables.

PubMed

Callens, D; Sarrazyn, R; Evens, W

2005-01-01

During three years, the new fungicide Signum, containing 6.7% pyraclostrobine + 26.7 % boscalid and developed by BASF. has been evaluated in leek, carrots and cabbages in several outdoor field experiments under practical conditions and during one year in outdoor lettuce. In leek, Phytophthora porri is one of the major leaf diseases causing lesions on differ ent places on the leaves, resulting in at least extra labour costs for trimming or even worse sometimes resulting in complete crop loss. So far, crop protection consists of repeated applications of fungicides especially during autumn and winter. Pyraclostrobin + boscalid has been evaluated in comparison with the fungicides mancozeb, mancozeb + metalaxyl-M and azoxystrobin. The progress of the disease during the growth season is discussed. For all parameters evaluated, pyraclostrobin + boscalid gave comparable or even better results than reference products. Especially during 2003, a small drop of the activity of benalaxyl against P. porri has been observed after repeated applications. In carrots, Erisiphe heraclei and Alternaria dauci are both the most common leaf diseases causing yield and quality loss. During periods of very high pressure of A. dauci, pyraclostrobin + boscalid, applied in a three weeks interval, revealed a superior activity compared with triazole references or compared with azoxystrobin. Against E. heraclei, a good control but also a clear dose response activity have been observed with pyraclostrobin + boscalid. Yield gain was approximately 30 ton /ha compared wih untreated. In Brussels sprouts, good efficacy was obtained against Mycosphaerella spp., Albugo candida and Alternaria spp. In outdoor lettuce Botrytis cinerea and Sclerotinia sclerotiorum are the most important diseases causing crop damage and reducing the quality of the heads. Pyraclostrobin + boscalid was evaluated in comparison with the standard fungicide iprodione. The plant protection was better with the new fungicide pyraclostrobin + boscalid.

Risk of cardiac disease and observations on lack of potential predictors by clinical history among children presenting for cardiac evaluation of mid-exertional syncope.

PubMed

Miyake, Christina Y; Motonaga, Kara S; Fischer-Colbrie, Megan E; Chen, Liyuan; Hanisch, Debra G; Balise, Raymond R; Kim, Jeffrey J; Dubin, Anne M

2016-06-01

This study aimed to evaluate the incidence of cardiac disorders among children with mid-exertional syncope evaluated by a paediatric cardiologist, determine how often a diagnosis was not established, and define potential predictors to differentiate cardiac from non-cardiac causes. Study design We carried out a single-centre, retrospective review of children who presented for cardiac evaluation due to a history of exertional syncope between 1999 and 2012. Inclusion criteria included the following: (1) age ⩽18 years; (2) mid-exertional syncope; (3) electrocardiogram, echocardiogram and an exercise stress test, electrophysiology study, or tilt test, with exception of long QT, which did not require additional testing; and (4) evaluation by a paediatric cardiologist. Mid-exertional syncope was defined as loss of consciousness in the midst of active physical activity. Patients with peri-exertional syncope immediately surrounding but not during active physical exertion were excluded. A total of 60 patients met the criteria for mid-exertional syncope; 32 (53%) were diagnosed with cardiac syncope and 28 with non-cardiac syncope. A majority of cardiac patients were diagnosed with an electrical myopathy, the most common being Long QT syndrome. In nearly half of the patients, a diagnosis could not be established or syncope was felt to be vasovagal in nature. Neither the type of exertional activity nor the symptoms or lack of symptoms occurring before, immediately preceding, and after the syncopal event differentiated those with or without a cardiac diagnosis. Children with mid-exertional syncope are at risk for cardiac disease and warrant evaluation. Reported symptoms may not differentiate benign causes from life-threatening disease.

Functional characterization of liver-associated lymphocytes in patients with liver metastasis.

PubMed

Winnock, M; Garcia-Barcina, M; Huet, S; Bernard, P; Saric, J; Bioulac-Sage, P; Gualde, N; Balabaud, C

1993-10-01

The liver-associated lymphocytes (LAL) population is mainly composed of cells with natural killer (NK) activity expressing the CD3+/-CD56+ phenotype. No evident difference has been found in the phenotypic data between patients with benign or malignant liver disease. In this study, the cytotoxic pattern of this population has been characterized from patients who underwent an operation for benign or metastatic liver disease. LAL were isolated by sinusoidal high-pressure lavage from partial hepatectomies. Phenotype was characterized by flow cytometry, and cytotoxicity was evaluated by standard 4-hour 51Cr release assays against NK and lymphokine-activated killer (LAK)-sensitive targets. In patients with benign liver disease, LAL showed spontaneous high levels of NK activity and LAK activity compared with peripheral blood lymphocytes. In patients with metastatic liver disease, no difference was observed in the levels of NK activity between LAL and peripheral blood, and the level of LAK activity was far lower than that expressed in patients with benign liver disease. These results show that the cytotoxic pattern of peripheral blood lymphocytes does not mirror that of LAL. In patients with benign liver disease, LAL are in a state of activation, whereas the decreased level of LAL cytotoxicity in patients with metastatic liver disease suggests that the cytotoxic activity of these cells could be inhibited by the presence of suppressive factors.

Increased body mass index in ankylosing spondylitis is associated with greater burden of symptoms and poor perceptions of the benefits of exercise.

PubMed

Durcan, Laura; Wilson, Fiona; Conway, Richard; Cunnane, Gaye; O'Shea, Finbar D

2012-12-01

Increased body mass index (BMI) in patients with ankylosing spondylitis (AS) is associated with a greater burden of symptoms and poor perceptions of the benefits of exercise. In AS, the effect of obesity on disease characteristics and exercise perceptions is unknown. We evaluated the prevalence of obesity in AS, to assess the attitudes of patients toward exercise and to evaluate the effect of obesity on symptoms and disease activity. Demographic data and disease characteristics were collected from 46 patients with AS. Disease activity, symptomatology, and functional disability were examined using standard AS questionnaires. BMI was calculated. Comorbidity was analyzed using the Charlson Comorbidity Index. Patients' attitudes toward exercise were assessed using the Exercise Benefits and Barriers Scale (EBBS). We compared the disease characteristics, perceptions regarding exercise, and functional limitations in those who were overweight to those who had a normal BMI. The mean BMI in the group was 27.4; 67.5% of subjects were overweight or obese. There was a statistically significant difference between those who were overweight and those with a normal BMI regarding their perceptions of exercise (EBBS 124.7 vs 136.6, respectively), functional limitation (Bath AS Functional Index 4.7 vs 2.5, Health Assessment Questionnaire 0.88 vs 0.26), and disease activity (Bath AS Disease Activity Index 4.8 vs 2.9). There was no difference between the groups in terms of their comorbid conditions or other demographic variables. The majority of patients in this AS cohort were overweight. They had a greater burden of symptoms, worse perceptions regarding the benefits of exercise, and enhanced awareness of their barriers to exercising. This is of particular concern in a disease where exercise plays a crucial role.

Pulmonary Function Test Abnormalities in Children With Inflammatory Bowel Disease: Is It Common?

PubMed

El Amrousy, Doaa Mohamed; Hassan, Samir; El-Ashry, Heba; Yousef, Mohamed; Sharshar, Ragia

2018-04-03

The aim of the study was to evaluate the frequency and type of pulmonary dysfunction in newly diagnosed children with inflammatory bowel disease (IBD) and the correlation between pulmonary function tests (PFTs) and IBD activity. It is an observational case-control study. One hundred newly diagnosed children with IBD were enrolled as the patient group, which was subdivided into 52 with Crohn disease (CD) and 48 with ulcerative colitis (UC). Fifty healthy children matched for age, sex, height, and body mass index (BMI) served as the control group. PFTs in the form of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, residual volume (RV), total lung capacity (TLC), mid-forced expiratory flow of 25% to 75% (FEF 25%-75%) and diffusing capacity of the lung for carbon monoxide (DLCO) were evaluated in all studied children. PFTs were measured at diagnosis, every 6 months for a period of 3 years, during remission and at least once during activity in patient group. There was significant progressive deterioration in all PFTs in IBD patients compared with their PFTs at the start of the study (P < 0.05) except for FEV1/FVC, RV, and TLC (P > 0.05). There was significant deterioration during disease activity compared with remission state regarding FEV1, FVC, FEV 25% to 75%, and DLCO (P < 0.05). Significant negative correlation was found between disease activity in both UC and CD groups and FEV1, FVC, FEV 25% to 75%, and DLCO. Subclinical PFT abnormalities are common in pediatric IBD even during remission period. So, periodic PFT evaluation should be considered in the routine follow-up of IBD children.

Assessment of activity limitations with the health assessment questionnaire predicts the need for support measures in patients with rheumatoid arthritis: a multicenter observational study.

PubMed

Janssens, Xavier; Decuman, Saskia; De Keyser, Filip

2014-01-01

This study investigated whether the Health Assessment Questionnaire (HAQ) can be used as an instrument to assess the need for social support measures that address activity limitations and participation issues in patients with rheumatoid arthritis (RA). This multicenter observational study included patients with RA and disease duration of at least one year, consulting their rheumatologist for routine evaluation of disease activity. In the single study visit data on demographics, disease history and current treatment were collected. DAS28 values were collected to evaluate current RA disease activity. Patients were asked to fill out the HAQ and SF-36 questionnaires. Receiver Operator Characteristics (ROC) curves were constructed to evaluate the performance of the HAQ, SF-36 and DAS28 in predicting the need for nine supporting measures available for chronically ill patients in the Belgian social security system. The expert opinion of the treating rheumatologist was used as a reference. The study included 316 patients with a mean age of 59.8 ± 12.6 years, disease duration of 11.4 ± 9.3 years, mean DAS28 values of 2.83 ± 1.17. Mean HAQ score was 0.95 ± 0.73, mean SF-36 score 56.5 ± 21.3. HAQ scores >1 were observed in 39.4% of patients. The area under the HAQ ROC curve was consistently >0.7 and higher for the HAQ than for SF-36 or DAS28 for all support measures. Rheumatologists on average recommended 3.67 support measures. The HAQ score was found to be a good predictor of the need for social support measures in patients with RA.

Development of ACRODAT®, a new software medical device to assess disease activity in patients with acromegaly.

PubMed

van der Lely, Aart J; Gomez, Roy; Pleil, Andreas; Badia, Xavier; Brue, Thierry; Buchfelder, Michael; Burman, Pia; Clemmons, David; Ghigo, Ezio; Jørgensen, Jens Otto Lunde; Luger, Anton; van der Lans-Bussemaker, Joli; Webb, Susan M; Strasburger, Christian J

2017-12-01

Despite availability of multimodal treatment options for acromegaly, achievement of long-term disease control is suboptimal in a significant number of patients. Furthermore, disease control as defined by biochemical normalization may not always show concordance with disease-related symptoms or patient's perceived quality of life. We developed and validated a tool to measure disease activity in acromegaly to support decision-making in clinical practice. An international expert panel (n = 10) convened to define the most critical indicators of disease activity. Patient scenarios were constructed based on these chosen parameters. Subsequently, a panel of 21 renowned endocrinologists at pituitary centers (Europe and Canada) categorized each scenario as stable, mild, or significant disease activity in an online validation study. From expert opinion, five parameters emerged as the best overall indicators to evaluate disease activity: insulin-like growth factor I (IGF-I) level, tumor status, presence of comorbidities (cardiovascular disease, diabetes, sleep apnea), symptoms, and health-related quality of life. In the validation study, IGF-I and tumor status became the predominant parameters selected for classification of patients with moderate or severe disease activity. If IGF-I level was ≤1.2x upper limit of normal and tumor size not significantly increased, the remaining three parameters contributed to the decision in a compensatory manner. The validation study underlined IGF-I and tumor status for routine clinical decision-making, whereas patient-oriented outcome measures received less medical attention. An Acromegaly Disease Activity Tool (ACRODAT) is in development that might assist clinicians towards a more holistic approach to patient management in acromegaly.

Defective Response of Natural Killer Activity to Thyroxine in Graves’ Disease

PubMed Central

Lee, Myung-Shik; Hong, Weon-Seon; Hong, Seong Woon; Lee, Jhin-Oh; Kang, Tae-Woong

1990-01-01

The effect of thyroxine (T4) on natural killer (NK) activity of peripheral blood lymphocytes (PBL) was investigated, using a 4-hr 51Cr release assay, in 18 patients with previously untreated Graves’ disease and in 18 controls. NK activity in patients with Graves disease was not significantly different from that in the controls. Normal T4 (NT) and high T4 (HT) medium, free T4 concentrations in which were 1.01 and 16.3 ng/dl, respectively, were used to evaluate the effect of T4 on NK activity. In the controls, NK activity increased in the NT or HT medium compared with that in the control medium at effector to target cell (E : T) ratios of 25 : 1 and 50 : 1. NK activity in the Graves’ disease patients, however, did not increase when either the NT or HT medium was used at E : T ratios of 25 : 1 and 50 : 1. These results suggest that patients with Graves’ disease have a similar NK activity to the controls but have a defect in the peripheral blood lymphocytes to increase NK activity in response to T4. PMID:2098098

Comparison of CT enterography and MR enterography imaging features of active Crohn disease in children and adolescents.

PubMed

Gale, Heather I; Sharatz, Steven M; Taphey, Mayureewan; Bradley, William F; Nimkin, Katherine; Gee, Michael S

2017-09-01

Assessment for active Crohn disease by CT enterography and MR enterography relies on identifying mural and perienteric imaging features. To evaluate the performance of established imaging features of active Crohn disease in children and adolescents on CT and MR enterography compared with histological reference. We included patients ages 18 years and younger who underwent either CT or MR enterography from 2007 to 2014 and had endoscopic biopsy within 28 days of imaging. Two pediatric radiologists blinded to the histological results reviewed imaging studies and scored the bowel for the presence or absence of mural features (wall thickening >3 mm, mural hyperenhancement) and perienteric features (mesenteric hypervascularity, edema, fibrofatty proliferation and lymphadenopathy) of active disease. We performed univariate analysis and multivariate logistic regression to compare imaging features with histological reference. We evaluated 452 bowel segments (135 from CT enterography, 317 from MR enterography) from 84 patients. Mural imaging features had the highest association with active inflammation both for MR enterography (wall thickening had 80% accuracy, 69% sensitivity and 91% specificity; mural hyperenhancement had 78%, 53% and 96%, respectively) and CT enterography (wall thickening had 84% accuracy, 72% sensitivity and 91% specificity; mural hyperenhancement had 76%, 51% and 91%, respectively), with perienteric imaging features performing significantly worse on MR enterography relative to CT enterography (P < 0.001). Mural features are predictors of active inflammation for both CT and MR enterography, while perienteric features can be distinguished better on CT enterography compared with MR enterography. This likely reflects the increased conspicuity of the mesentery on CT enterography and suggests that mural features are the most reliable imaging features of active Crohn disease in children and adolescents.

Gallium-68 DOTA-NOC PET/CT as an alternate predictor of disease activity in sarcoidosis.

PubMed

Sharma, Sanchit; Singh, Achintya D; Sharma, Surendra K; Tripathi, Madhavi; Das, Chandan J; Kumar, Rajeev

2018-05-30

We evaluated the role of gallium-68-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-octreotide (Ga-DOTA-NOC) PET/CT in assessing sarcoidosis disease activity. Patients diagnosed with sarcoidosis underwent Ga-DOTA-NOC-PET/CT. The maximum standardized uptake value (SUVmax) at the pathological site and in the descending thoracic aorta (reference standard, SUVmed) were assessed. A SUVmax/SUVmed ratio (disease activity score) of more than one was considered a marker of active disease and was compared with the clinical symptoms and serum angiotensin-converting enzyme and computed tomography (CT) scan. The primary outcome was to assess the efficacy of the scan in estimating disease activity. Of the 39 patients enrolled in the study, 27 patients were symptomatic and the rest were asymptomatic at enrollment. Increased disease activity was present in 25 (92%) of the 27 symptomatic patients and two (16%) of the 12 asymptomatic patients. The sensitivity and specificity of the test were 92.5% (95% confidence interval=75.7-99.0) and 83.3% (95% confidence interval=51.5-97.9), respectively. Seven out of nine patients who became asymptomatic after treatment showed a significant decrease in the mean disease activity score in post-treatment scans (3.38±1.05 vs 1.20±0.82, P<0.001). Ga-DOTA-NOC PET/CT emerged as a useful tool to assess the disease activity and treatment response in patients with sarcoidosis with thoracic involvement.

Adalimumab with Methotrexate in Treatment-Naïve Japanese Patients with Rheumatoid Arthritis at Risk of Progressive Structural Joint Damage: A Postmarketing Observational Study.

PubMed

Ito, Yukiko; Hozumi, Kaori; Okada, Yukiko; Kurimoto, Sarina

2017-06-01

The objective of this study was to evaluate the real-world safety and effectiveness of adalimumab with methotrexate (MTX) in disease-modifying antirheumatic drug (DMARD)- and biologic-naïve Japanese patients with rheumatoid arthritis (RA) at risk of progressive structural joint damage. This multicenter, prospective, observational, postmarketing surveillance study was conducted between February 2013 and April 2015 at 84 centers in Japan. Patients with RA at risk of progressive structural joint damage were enrolled and initiated treatment with adalimumab and MTX. Adverse events were recorded up to week 28. Effectiveness/disease activity was assessed using the Disease Activity Score based on a 28-joint count with erythrocyte sedimentation rate and C-reactive protein (DAS28-4ESR and DAS28-4CRP), Clinical Disease Activity Index, and Simplified Disease Activity Index at 0, 4, 12, and 24 weeks. DAS28-4CRP response was evaluated in the low-dose (<8 mg/week) and high-dose (≥8 mg to ≤16 mg/week) MTX groups at week 24. One hundred fifty-seven of 163 patients comprised the safety cohort: mean (SD) age, 56.5 (13.9) years; females, 65.6%; rheumatoid factor positive, 73.2%; anti-cyclic citrullinated peptide antibody positive, 66.9%; bone erosions, 51.6%; mean disease duration, 9.5 months. The majority of patients (≥80%) had moderate or high disease activity at baseline, and ≥50% with available data achieved remission or low disease activity at week 24 (DAS28-4CRP <3.2). Five serious adverse drug reactions occurred in four patients, including pyelonephritis, Pneumocystis jiroveci pneumonia, interstitial lung disease, pleurisy, and pericarditis; the outcomes were either recovered or recovering. Significant improvements/reductions in disease activity over 24 weeks were noted in all effectiveness measures (P < 0.0001). Most of the population achieved DAS28-4CRP remission (<2.6) at week 24 regardless of the MTX dose. Adalimumab in combination with MTX could be a beneficial treatment option for DMARD- and biologic-naïve Japanese patients with RA at risk of progressive structural joint damage. AbbVie GK and Eisai. ClinicalTrials.gov identifier, NCT01783730.

National and international veterinary reference laboratories for infectious diseases.

PubMed

Edwards, S; Alexander, D

1998-08-01

Reference laboratories play an increasingly important role in the harmonisation of laboratory diagnostic tests and the standardisation of veterinary vaccines. This is particularly important in building confidence between international trading partners. The authors review aspects of the organisation, designation and support of reference laboratories for infectious diseases of animals and discuss the principal activities which such laboratories would normally perform. These activities include advice and consultancy, publications and communication, training, research, disease surveillance, maintenance of culture collections, evaluation of reference methods, preparation of reference materials and organisation of inter-laboratory comparisons.

The relationship between disease activity, quality of life, and personality types in rheumatoid arthritis and ankylosing spondylitis patients.

PubMed

Donisan, T; Bojincă, V C; Dobrin, M A; Bălănescu, D V; Predețeanu, D; Bojincă, M; Berghea, F; Opriș, D; Groșeanu, L; Borangiu, A; Constantinescu, C L; Ionescu, R; Bălănescu, A R

2017-07-01

We hypothesized that clinical outcomes might be influenced by personality type (A, B, C, D) in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). One hundred ninety-four patients (104 with RA, 90 with AS) participated in a questionnaire study. We evaluated health-related quality of life (HRQoL) using the Medical Outcome Study Short-Form 36 (SF-36), personality type A/B with the Jenkins Activity Survey, type C with the State-Trait Anger Expression Inventory Anger-in Scale, type D with the Type D Personality Scale, and disease activity with Disease Activity Score with 28 joints for RA and Bath Ankylosing Spondylitis Disease Activity Index for AS. We used Pearson's correlation coefficient, independent samples t tests, and multivariate analyses of variance. In the RA group, type D personality was significantly correlated with 7/12 SF-36 components. AS patients with type D personality had deficits in all SF-36 subscales. Type D was related with higher disease activity in RA and AS. Both RA and AS type C patients had more active disease forms and negatively affected HRQoL subscales. In the RA group, type A personality did not correlate with HRQoL, but it positively influenced pain visual analog scale scores. In AS patients, type A personality was linked with higher HRQoL and with less active disease. Type C and type D personality types were correlated with decreased HRQoL and higher disease activity in RA and AS patients. Type A personality was associated with less active disease and higher HRQoL in AS patients and with less pain in RA patients.

Total flavonoid content and formulation antioxidant cream stem of jatropha multifida l.

NASA Astrophysics Data System (ADS)

Dwi Franyoto, Yuvianti; Kusmita, Lia; Mutmainah; Demma Angrena, Riega

2018-05-01

Free radical induced oxidative stress that influences the occurrence of various degenerative diseases such as cancer, coronary heart disease and premature aging. Stems of Jatropha multifida L are known to contain flavanoid compounds have antioxidant activity. A study has been carried out to determine antioxidant potential of stems of Jatropha multifida L. Initially, material was macerated gradually with ethanol. The extract obtained was filtered and evaporated. Determination of total flavanoid contents (TFC) using spectrophotometric methods. The antioxidant potential of this extract was evaluated by 2, 2-diphenyl-1- picrylhydrazyl (DPPH) radical scavenging assay. In the DPPH radical-scavenging activities, the extract had the antioxidant activity (IC50 = 72 ± 0.01 μg/ml). The results showed the extracts of Jatropha multifida L. could be considered as natural antioxidants and may be useful for curing diseases arising from oxidative deterioration. The formulation comprises with 5% of extract and was formulated using fusion method. The evaluation of the formulated cream showed good results and can be good potential for cosmetic product development.

Large Renal Corpuscle: Clinical Significance of Evaluation of the Largest Renal Corpuscle in Kidney Biopsy Specimens.

PubMed

Kataoka, Hiroshi; Mochizuki, Toshio; Nitta, Kosaku

2018-01-01

Renal prognostic factors of chronic kidney disease are important concerns for patients. Kidney biopsy can be used to evaluate not only the activity of the original disease but also various risk factors related to the lifestyle of patients. Considering that lifestyle-related factors, including obesity and metabolic syndrome, are crucial prognostic risk factors of kidney disease progression and all-cause mortality, evaluation of lifestyle-related prognostic factors in kidney biopsy of all kidney diseases is important. Renal corpuscle size (glomerular size) is an easily measured parameter and potentially acts as a predictor of long-term renal function. Large renal corpuscle found on kidney biopsy is a classic and simple indicator, and has merit owing to its quantitative nature, but it has yet to be used to its full potential in clinical settings. Large renal corpuscle is an index that includes not only the activity of the original disease but also the damage of various metabolic risk states as represented by obesity, diabetes, and metabolic syndrome. Large renal corpuscles could be used to guide therapy. In this review, after identifying the pitfalls regarding the assessment of mean values in medical research, we propose that measurement of the maximum renal corpuscle profile (glomerular profile) in renal biopsies would provide valuable insights into the diagnosis, prognosis, and management of kidney diseases. © 2018 S. Karger AG, Basel.

Comparison of the Farr radioimmunoassay, 3 commercial enzyme immunoassays and Crithidia luciliae immunofluorescence test for diagnosis and activity assessment of systemic lupus erythematosus.

PubMed

Launay, David; Schmidt, Jean; Lepers, Sébastien; Mirault, Tristan; Lambert, Marc; Kyndt, Xavier; Reumaux, Dominique; Duhamel, Alain; Hachulla, Eric; Hatron, Pierre-Yves; Prin, Lionel; Dubucquoi, Sylvain

2010-07-04

Among anti-double-strand (ds)DNA antibody assays, Farr radioimmunoassay is decreasingly used because it requires radioactive material and is labor intensive. We evaluated the performance of Farr, three commercial enzyme immunoassays (EIAs) and the Crithidia luciliae immunofluorescence test (CLIFT) in systemic lupus erythematosus (SLE). Anti-dsDNA antibodies were determined in 99 SLE patients, 101 healthy subjects, and 53 patients with autoimmune rheumatic diseases. Farr performed better than the 3 EIAs and CLIFT for the diagnosis of SLE at the manufacturer's cut off and at the cut off set to achieve a specificity of 95%. To achieve a similar level of specificity, some EIAs had a decrease in sensitivity which was dramatic for some tests. Farr was also the best at distinguishing patients with quiescent to mildly active disease from patients with more active disease at the cut off value of 93 IU/ml. Using manufacturer's cut off did not allow distinguishing between patients with quiescent and active SLE. Farr was the best global test to assess the level of anti-dsDNA antibodies for both diagnosis and disease activity evaluation in SLE with adequately determined cut off values. Some EIA had low performances limiting their use in decision-making regarding diagnosis and/or treatment. Copyright 2010 Elsevier B.V. All rights reserved.

Guidelines for the field evaluation of desert tortoise health and disease

USGS Publications Warehouse

Berry, Kristin H.; Christopher, Mary M.

2001-01-01

Field evaluation of free-ranging wildlife requires the systematic documentation of a variety of environmental conditions and individual parameters of health and disease, particularly in the case of rare or endangered species. In addition, defined criteria are needed for the humane salvage of ill or dying animals. The purpose of this paper is to describe, in detail, the preparation, procedures, and protocols we developed and tested for the field evaluation of wild desert tortoises (Gopherus agassizii). These guidelines describe: preparations for the field, including developing familiarity with tortoise behavior and ecology, and preparation of standardized data sheets; journal notes to document background data on weather conditions, temperature, rainfall, locality, and historic and recent human activities; procedures to prevent the spread of disease and parasites; data sheets for live tortoises to record tortoise identification, location, sex, body measurements and activity; health profile forms for documenting and grading physical abnormalities of tortoise posture and movements, general condition (e.g., lethargy, cachexia), external parasites, and clinical abnormalities associated with shell and upper respiratory diseases; permanent photographic records for the retrospective analysis of progression and regression of upper respiratory and eye diseases, analysis of shell lesions and evaluation of growth and age; and indications and methods for salvaging ill or dying tortoises for necropsy evaluation. These guidelines, tested on 5,000 to 20,000 tortoises over a 10 to 27 yr period, were designed to maximize acquisition of data for demographic, ecological, health and disease research projects; to reduce handling and stress of individual animals; to avoid spread of infectious disease; to promote high quality and consistent data sets; and to reduce the duration and number of field trips. The field methods are adapted for desert tortoise life cycle, behavior, anatomy, physiology, and pertinent disease; however the model is applicable to other species of reptiles. Comprehensive databases of clinical signs of disease and health are crucial to research endeavors and essential to decisions on captive release, epidemiology of disease, translocation of wild tortoises, breeding programs, and euthanasia.

Novel Nrf2 activators from microbial transformation products inhibit blood-retinal barrier permeability in rabbits.

PubMed

Nakagami, Yasuhiro; Masuda, Kayoko; Hatano, Emiko; Inoue, Tatsuya; Matsuyama, Takuya; Iizuka, Mayumi; Ono, Yasunori; Ohnuki, Takashi; Murakami, Yoko; Iwasaki, Masaru; Yoshida, Kazuhiro; Kasuya, Yuji; Komoriya, Satoshi

2015-03-01

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes encoding many antioxidant enzymes and phase II detoxifying enzymes. Activation of the Nrf2 pathway seems protective for many organs, and although a well-known Nrf2 activator, bardoxolone methyl, was evaluated clinically for treating chronic kidney disease, it was found to induce adverse events. Many bardoxolone methyl derivatives, mostly derived by chemical modifications, have already been studied. However, we adopted a biotransformation technique to obtain a novel Nrf2 activator. The potent novel Nrf2 activator, RS9, was obtained from microbial transformation products. Its Nrf2 activity was evaluated by determining NADPH:quinone oxidoreductase-1 induction activity in Hepa1c1c7 cells. We also investigated the effects of RS9 on oxygen-induced retinopathy in rats and glycated albumin-induced blood-retinal barrier permeability in rabbits because many ocular diseases are associated with oxidative stress and inflammation. Bardoxolone methyl doubled the specific activity of Nrf2 in Hepa1c1c7 cells at a much higher concentration than RS9. Moreover, the induction of Nrf2-targeted genes was observed at a one-tenth lower concentration of RS9. Interestingly, the cytotoxicity of RS9 was substantially reduced compared with bardoxolone methyl. Oral and intravitreal administration of RS9 ameliorated the pathological scores and leakage in the models of retinopathy in rats and ocular inflammation in rabbits respectively. Nrf2 activators are applicable for treating ocular diseases and novel Nrf2 activators have potential as a unique method for prevention and treatment of retinovascular disease. © 2014 The British Pharmacological Society.

Novel Nrf2 activators from microbial transformation products inhibit blood–retinal barrier permeability in rabbits

PubMed Central

Nakagami, Yasuhiro; Masuda, Kayoko; Hatano, Emiko; Inoue, Tatsuya; Matsuyama, Takuya; Iizuka, Mayumi; Ono, Yasunori; Ohnuki, Takashi; Murakami, Yoko; Iwasaki, Masaru; Yoshida, Kazuhiro; Kasuya, Yuji; Komoriya, Satoshi

2015-01-01

Background and Purpose Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes encoding many antioxidant enzymes and phase II detoxifying enzymes. Activation of the Nrf2 pathway seems protective for many organs, and although a well-known Nrf2 activator, bardoxolone methyl, was evaluated clinically for treating chronic kidney disease, it was found to induce adverse events. Many bardoxolone methyl derivatives, mostly derived by chemical modifications, have already been studied. However, we adopted a biotransformation technique to obtain a novel Nrf2 activator. Experimental Approach The potent novel Nrf2 activator, RS9, was obtained from microbial transformation products. Its Nrf2 activity was evaluated by determining NADPH:quinone oxidoreductase-1 induction activity in Hepa1c1c7 cells. We also investigated the effects of RS9 on oxygen-induced retinopathy in rats and glycated albumin-induced blood–retinal barrier permeability in rabbits because many ocular diseases are associated with oxidative stress and inflammation. Key Results Bardoxolone methyl doubled the specific activity of Nrf2 in Hepa1c1c7 cells at a much higher concentration than RS9. Moreover, the induction of Nrf2-targeted genes was observed at a one-tenth lower concentration of RS9. Interestingly, the cytotoxicity of RS9 was substantially reduced compared with bardoxolone methyl. Oral and intravitreal administration of RS9 ameliorated the pathological scores and leakage in the models of retinopathy in rats and ocular inflammation in rabbits respectively. Conclusion and Implications Nrf2 activators are applicable for treating ocular diseases and novel Nrf2 activators have potential as a unique method for prevention and treatment of retinovascular disease. PMID:25363737

Validation of the "German Inflammatory Bowel Disease Activity Index (GIBDI)": An Instrument for Patient-Based Disease Activity Assessment in Crohn's Disease and Ulcerative Colitis.

PubMed

Hüppe, Angelika; Langbrandtner, Jana; Häuser, Winfried; Raspe, Heiner; Bokemeyer, Bernd

2018-05-09

 Assessment of disease activity in Crohn's disease (CD) and ulcerative colitis (UC) is usually based on the physician's evaluation of clinical symptoms, endoscopic findings, and biomarker analysis. The German Inflammatory Bowel Disease Activity Index for CD (GIBDI CD ) and UC (GIBDI UC ) uses data from patient-reported questionnaires. It is unclear to what extent the GIBDI agrees with the physicians' documented activity indices.  Data from 2 studies were reanalyzed. In both, gastroenterologists had documented disease activity in UC with the partial Mayo Score (pMS) and in CD with the Harvey Bradshaw Index (HBI). Patient-completed GIBDI questionnaires had also been assessed. The analysis sample consisted of 151 UC and 150 CD patients. Kappa coefficients were determined as agreement measurements.  Rank correlations were 0.56 (pMS, GIBDI UC ) and 0.57 (HBI, GIBDI CD ), with p < 0.001. The absolute agreement for 2 categories of disease activity (remission yes/no) was 74.2 % (UC) and 76.6 % (CD), and for 4 categories (none/mild/moderate/severe) 60.3 % (UC) and 61.9 % (CD). The kappa values ranged between 0.47 for UC (2 categories) and 0.58 for CD (4 categories).  There is satisfactory agreement of GIBDI with the physician-documented disease activity indices. GIBDI can be used in health care research without access to assessments of medical practitioners. In clinical practice, the index offers a supplementary source of information. © Georg Thieme Verlag KG Stuttgart · New York.

[Perceived pain and weather changes in rheumatic patients].

PubMed

Miranda, L Cunha; Parente, M; Silva, C; Clemente-Coelho, P; Santos, H; Cortes, S; Medeiros, D; Ribeiro, J Saraiva; Barcelos, F; Sousa, M; Miguel, C; Figueiredo, R; Mediavilla, M; Simões, E; Silva, M; Patto, J Vaz; Madeira, H; Ferreira, J; Micaelo, M; Leitão, R; Las, V; Faustino, A; Teixeira, A

2007-01-01

Rheumatic patients with chronic pain describe in a vivid way the influence of climate on pain and disease activity. Several studies seem to confirm this association. To evaluate and compare in a population of rheumatic patients the perceived influence of weather changes on pain and disease activity This is a retrospective cross-sectional study. For three weeks an assisted self-reported questionnaire with nine dimensions and a VAS pain scale was performed on consecutive out-patients in our clinic. 955 patients 787 female 168 male mean age 57.9 years with several rheumatologic diagnosis were evaluated. Overall 70 of the patients believed that the weather influenced their disease and 40 believed that the influence was high. Morning stiffness was influenced in 54 high influenced in 34 . Autumn and Winter were the most influential periods as well as humidity 67 and low temperatures 59 . In our study as well as in literature we found that a high percentage of patients 70 perceived that weather conditions influenced their pain and disease. Fibromyalgia patients seemed to be strongly influenced by weather changes. Our study confirms that patients perception on the influence of climate on pain and therefore their disease is an important clinical factor and it should be considered when evaluating rheumatic patients.

Serum interleukin measurement may help identify thyroid cancer patients with active disease.

PubMed

Martins, Mariana Bonjiorno; Marcello, Marjory Alana; Batista, Fernando de Assis; Peres, Karina Colombera; Meneghetti, Murilo; Ward, Mirela Andrea Latham; Etchebehere, Elba Cristina Sá de Camargo; da Assumpção, Ligia Vera Montali; Ward, Laura Sterian

2018-02-01

Investigate the clinical utility of serum interleukin dosages of IL-2, IL-2R, IL-4, IL-6, IL-6R, IL-8, IL-10 and IL-12 in the diagnosis and characterization of patients with DTC. In particular, verify ILs utility in the identification of individuals who are evolving disease-free or with the active disease. We evaluated 200 patients with malignant nodules (100 patients disease-free and 100 patients with recurrence/active disease); 60 benign nodules and 100 healthy controls, serum levels were assessed by ELISA. All ILs, but not IL-4, differentiated these three groups. We observed that IL-2, 2R and 10 serum concentrations were associated with thyroglobulin levels. Serum IL-2 was able to differentiate patients with active disease from the disease-free with a sensitivity of 98%, specificity of 58%, positive predictive value (PPV) of 70% and negative predictive value (NPV) of 97% (p=0.0007). IL-6R levels differentiated patients with active disease from the disease-free patients with 56% sensitivity, 63% specificity, PPV of 60% and NPV of 59% (p<0.0001). IL-8 values also distinguished patients with active disease from the disease-free ones with sensitivity of 50%, specificity of 76%, PPV of 68% and NPV of 60% (p=0.0025); using IL-12, we obtained a sensitivity value of 73%, specificity of 66%, PPV of 68% and NPV of 71% (p<0.0001). Furthermore, interleukin levels showed association with some tumor characteristics of aggressiveness. We suggest that the serum concentration of ILs may assist in the diagnosis and characterization of tumor malignancy helping identify patients with active disease who deserve closer medical attention. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of down-titration versus continuation strategies of biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis with low disease activity or in remission: a systematic review and meta-analysis.

PubMed

Jiang, Mei; Ren, Feifeng; Zheng, Yaning; Yan, Ruyu; Huang, Wenhan; Xia, Ning; Luo, Lei; Zhou, Jun; Tang, Lin

2017-01-01

To evaluate the efficacy and safety of down-titration (dose reduction/tapering) strategies compared with continuation of biological disease-modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who achieved and maintained low disease activity or remission. We searched the following electronic database up to March 2016: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and conference proceedings of the American College of Rheumatology (ACR) and European League against Rheumatism (EULAR). Our meta-analysis included randomized controlled trials (RCTs) of RA patients with low disease activity or in remission that compared down-titration treatment with continuation treatment. Data on flare, defined as a 28-joint Disease Activity Score of ≥3.2, had to have been reported. Outcomes on efficacy or safety were collected. Of 1136 references identified, five RCTs (total, 771 participants) were included. The incidence of disease relapse in the down-titration and continuation groups was similar (risk ratio (RR)=1.14, 95% CI=0.88-1.49). There was no statistical difference in the number of serious adverse events (RR=1.15, 95% CI=0.53-2.49). Withdrawals due to inefficacy or toxicity were similar between groups and no clinically meaningful difference in efficacy outcomes was observed by continuation treatment. Our findings indicated that continuing a standard dose of biological DMARDs in patients with low disease activity conveyed no significant benefit as compared with down-titration therapy, suggesting that a down-titration strategy is as effective as a continuation strategy. Since the number of trials meeting the criteria for this meta-analysis was relatively low, future analyses with additional prospective RCTs are required to compare other biological agents and evaluate the long-term efficacy of these two strategies.

Norrie disease gene is distinct from the monoamine oxidase genes

PubMed Central

Sims, Katherine B.; Ozelius, Laurie; Corey, Timothy; Rinehart, William B.; Liberfarb, Ruth; Haines, Jonathan; Chen, Wei Jane; Norio, Reijo; Sankila, Eeva; de la Chapelle, Albert; Murphy, Dennis L.; Gusella, James; Breakefield, Xandra O.

1989-01-01

The genes for MAO-A and MAO-B appear to be very close to the Norrie disease gene, on the basis of loss and /or disruption of the MAO genes and activities in atypical Norrie disease patients deleted for the DXS7 locus; linkage among the MAO genes, the Norrie disease gene, and the DXS7 locus; and mapping of all these loci to the chromosomal region Xp11. The present study provides evidence that the MAO genes are not disrupted in “classic” Norrie disease patients. Genomic DNA from these “nondeletion” Norrie disease patients did not show rearrangements at the MAOA or DXS7 loci. Normal levels of MAO-A activities, as well as normal amounts and size of the MAO-A mRNA, were observed in cultured skin fibroblasts from these patients, and MAO-B activity in their platelets was normal. Catecholamine metabolites evaluated in plasma and urine were in the control range. Thus, although some atypical Norrie disease patients lack both MAO-A and MAO-B activities, MAO does not appear to be an etiologic factor in classic Norrie disease. ImagesFigure 2Figure 3 PMID:2773935

Disease course and long-term outcome of juvenile localized scleroderma: Experience from a single pediatric rheumatology Centre and literature review.

PubMed

Martini, Giorgia; Fadanelli, Gloria; Agazzi, Anna; Vittadello, Fabio; Meneghel, Alessandra; Zulian, Francesco

2018-05-03

Juvenile Localized Scleroderma (JLS) is a rare disorder that may cause severe aesthetic sequelae and functional disability. To date, data on natural history and long-term outcome are discordant and difficult to compare due to the heterogeneity of clinical subtypes, treatments and methods to evaluate activity and outcome in previous studies. A retrospective and cross-sectional study including 133 patients followed between January 1991 and December 2016 was conducted at our Pediatric Rheumatology Centre. Disease course was drawn by retrospective analysis of patients' clinical features, treatment, disease course and outcome at the last evaluation. Disease activity and severity of tissue damage were assessed by using parameters derived from the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) and thermography. Most patients achieved complete remission, as only 12.5%, all with the linear subtype, had still active disease after over 10 years of follow-up. At least one disease relapse occurred in 22.2% of patients and first flare was observed 20 months after first treatment discontinuation. Mild tissue damage was observed in more than half of patients, in 25.4% was moderate and in 23.0% severe; 19.8% presented a functional limitation. The entity of skin and subcutaneous fat loss established at the early stages of the disease as 27.8% of patients with shorter disease duration had severe damage and the rates remained constant in patients with longer follow-up. The delay in start of systemic treatment was associated with longer disease activity and higher relapse rate. Patients with linear scleroderma (LS), pansclerotic morphea (PM) and mixed subtype (MS) presented more severe aesthetic and functional damage but did not differ from other subtypes as for rate of complete remission. JLS in some patients can be a very aggressive disease with persistent activity after >10 years and/or several disease relapses. As tissue damage establishes early in disease course a prompt diagnosis and start of appropriate treatment is crucial to control inflammation, to limit and stabilize damage, before it become irreversible. Clinicians must be aware that children with JLS may present disease reactivation so it is important to closely follow-up patients, particularly in the first 2 years after discontinuation of treatment when disease relapses may occur more frequently. Copyright © 2018 Elsevier B.V. All rights reserved.

Communities putting prevention to work: Local evaluation of community-based strategies designed to make healthy living easier☆,☆☆

PubMed Central

Soler, Robin E.; Whitten, Kathleen L.; Ottley, Phyllis G.

2015-01-01

This introduction is an overview of the articles presented in this supplement that describe implementation and evaluation activities conducted as part of the Centers for Disease Control and Prevention’s (CDC’s) Communities Putting Prevention to Work (CPPW) initiative. CPPW was one of the largest federal investments ever to combat chronic diseases in the United States. CPPW supported high-impact, jurisdiction-wide policy, systems, and environmental changes to improve health by increasing access to physical activity and healthy foods, and by decreasing tobacco use and exposure to secondhand smoke. The articles included in this supplement describe implementation and evaluation efforts of strategies implemented as part of CPPW by local awardees. This supplement is intended to guide the evidence base for public health interventions on the basis of jurisdiction-wide policy and environmental-level improvements and to encourage rigorous evaluation of the public health interventions. PMID:25150384

The impact of temperature and precipitation on blacklegged tick activity and Lyme disease incidence in endemic and emerging regions.

PubMed

Burtis, James C; Sullivan, Patrick; Levi, Taal; Oggenfuss, Kelly; Fahey, Timothy J; Ostfeld, Richard S

2016-11-25

The incidence of Lyme disease shows high degrees of inter-annual variation in the northeastern United States, but the factors driving this variation are not well understood. Complicating matters, it is also possible that these driving factors may vary in regions with differing histories of Lyme disease endemism. We evaluated the effect of the number of hot (T > 25 °C), dry (precipitation = 0) days during the questing periods of the two immature Ixodes scapularis life stages (larval and nymphal) on inter-annual variation in Lyme disease incidence between 2000 and 2011 in long-term endemic versus recently endemic areas. We also evaluated the effect of summer weather on tick questing activity and the number of ticks found on small mammals between 1994 and 2012 on six sites in Millbrook, NY. The number of hot, dry days during the larval period of the previous year did not affect the human incidence of Lyme disease or the density of questing nymphs the following season. However, dry summer weather during the nymphal questing period had a significant negative effect on the incidence of Lyme disease in the long-term endemic areas, and on the density of questing nymphs. Summer weather conditions had a more pronounced effect on actively questing I. scapularis collected via dragging than on the number of ticks found feeding on small mammals. In recently endemic areas Lyme disease incidence increased significantly over time, but no trend was detected between disease incidence and dry summer weather. Recently endemic regions showed an increase in Lyme disease incidence over time, while incidence in long-term endemic regions appears to have stabilized. Only within the stabilized areas were we able to detect reduced Lyme disease incidence in years with hot, dry summer weather. These patterns were reflected in our field data, which showed that questing activity of nymphal I. scapularis was reduced by hot, dry summer weather.

Ultrasound resistive index, power Doppler, and clinical parameters in established rheumatoid arthritis.

PubMed

Bisi, Melissa Cláudia; do Prado, Aline Defaveri; Piovesan, Deise Marcela; Bredemeier, Markus; da Silveira, Inês Guimarães; Mendonça, José Alexandre; Staub, Henrique Luiz

2017-04-01

Ultrasonography (US) is a useful tool for the evaluation of sinovial vascularization and proliferation in rheumatoid arthritis (RA). Accordingly, resistive index (RI) on spectral Doppler (sD) US provides a quantitative analysis of vascular inflammation, but its utility in the evaluation of RA activity has not been established. Our objective was to determine the association of RI with other US parameters of synovitis and with clinical disease activity in established RA. Patients with positive power Doppler (pD) were included in a prospective cross-sectional study. Disease activity and disability were evaluated using the Disease Activity Score in 28-joints (DAS28) and Health Assessment Questionnaire (HAQ), respectively. Gray scale (GS) synovitis, pD, and sD analyses were performed by one of two examiners in wrists and the second and third metacarpophalangeal and proximal interphalangeal joints. The 10-joint GS and 10-joint pD scores and mean RI were then calculated. Weighted kappa (WK) values were employed to assess interobserver reability, and correlations were tested using the Spearman coefficient. Ninety-five RA patients (median duration of disease of 7 years and mean DAS28 of 4.32 ± 1.66) were included. WK values in real-time US were 0.77 for synovitis, 0.87 for pD, and 0.68 for RI. There were no significant correlations of RI with 10-joint GS, 10-joint pD, DAS28, joint counts, or HAQ (P > 0.10 for all tests). Patients in remission had a mean RI similar to those with high disease activity (0.62 ± 0.10, n = 15 versus 0.63 ± 0.13, n = 34, respectively). The addition of the RI score did not seem to improve US performance in patients with established RA.

[Using cluster analysis for evaluation of sensitivity to antibiotics of pathogens isolated from women with genital inflammatory diseases].

PubMed

Tsyganenko, A Ia; Kon', E V

2007-01-01

The study was conducted to evaluate sensitivity to 44 antibiotics of pathogens isolated from 183 women with genital inflammatory diseases and to offer schemes of antibacterial treatment. The pathogens (66.8%) were in associations. The probability of isolation of main bacteria and sexually transmitted microorganisms in different associations was estimated in the work. Using the methods of clustering analysis all the tested antibiotics were divided into 3 groups, depending on their antimicrobial activity toward bacteria isolated both in monoculture and in associations. Furagin, cefotaxime, gentamicin, cefoperazon, ceftriaxon, ciprofloxacin, pefloxacin, as well as, cefazolin, zoxan, ofloxacin, and lomefloxacin were shown to be the most effective antibiotics in vitro. The least activity was diplayed by ectericid, chlorophillipt, and ampiox. These data should be considered when choosing the antibacterial treatment of genital inflammatory diseases.

Serum amyloid A protein in amyloidosis, rheumatic, and neoplastic diseases

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

Benson, M.D.; Cohen, A.S.

1979-01-01

Serum levels of amyloid protein A (SAA) have been shown to be elevated in different types of amyloidosis and in rheumatic diseases by radioimmunoassay using 125 iodine labeled AA and anti-AA. SAA levels were elevated in both primary and secondary amyloidosis, but there were highly significant differences between these levels. In heredofamilial amyloid, SAA levels were within normal limits. While the mean SAA level was elevated in persons over 70 years, the fact that some persons in this age group had normal levels suggested that marked elevation after age 70 may be due to occult inflammatory or neoplastic disease. Highmore » SAA levels in patients with rheumatoid arthritis correlated, in most cases, with physician evaluation of disease activity and Westergren ESR. SAA levels in patients with systemic lupus erythematosus were lower than those in patients with rheumatoid arthritis, and most patients with degenerative joint disease had normal levels. Very high levels of SAA were found in patients with neoplastic diseases. Patients with carcinoma of the lung and bowel had much higher levels than patients with carcinoma of the breast. Determination of SAA levels may be of value in evaluating different forms of systemic amyloidosis, assessing the activity of rheumatic disease, and screening for occult inflammatory or neoplastic disease.« less

Psoriasis and psoriatic arthritis in African-American patients--the need to measure disease burden.

PubMed

Kerr, Gail S; Qaiyumi, Seema; Richards, John; Vahabzadeh-Monshie, Hashem; Kindred, Chesahna; Whelton, Sean; Constantinescu, Florina

2015-10-01

Gaps in knowledge exist regarding the clinical characteristics of psoriatic disease in ethnic minority patients. We evaluated validated clinical disease measures of psoriasis and psoriatic arthritis in African-American and Caucasian patients. Adult outpatients with confirmed diagnoses of psoriasis and psoriatic arthritis and seen at four urban academic institutions were eligible for evaluation. Validated patient and physician-reported disease outcome parameters, quality of life measures of psoriasis and psoriatic arthritis, and frequencies of systemic immunosuppressive therapies and patient comorbidities were documented. Psoriatic arthritis was less frequent in African-Americans compared to Caucasians (30 vs. 64.5 %, respectively, p < 0.001); however, African-Americans had more severe skin involvement [Psoriasis Area and Severity Index 8.4 (10.0) vs. Caucasians 5.5 (6.4), p = 0.06], with greater psychological impact and impaired quality of life. Use of biologic therapies was greater in Caucasian patients (46.2 vs. 13.3 % in African-Americans, p < 0.0001); yet, only one in four patients of the study cohort achieved minimal disease activity. Comorbidity was not associated with frequency of immunosuppressive drug use. In order to achieve a target of low disease activity and to reduce ethnic disparities in the care of psoriatic disease, the routine application of measures of disease status is needed.

Immunoregulatory mechanisms in Chagas disease: modulation of apoptosis in T-cell mediated immune responses.

PubMed

Chaves, Ana Thereza; de Assis Silva Gomes Estanislau, Juliana; Fiuza, Jacqueline Araújo; Carvalho, Andréa Teixeira; Ferreira, Karine Silvestre; Fares, Rafaelle Christine Gomes; Guimarães, Pedro Henrique Gazzinelli; de Souza Fagundes, Elaine Maria; Morato, Maria José; Fujiwara, Ricardo Toshio; da Costa Rocha, Manoel Otávio; Correa-Oliveira, Rodrigo

2016-04-30

Chronic Chagas disease presents different clinical manifestations ranging from asymptomatic (namely indeterminate) to severe cardiac and/or digestive. Previous results have shown that the immune response plays an important role, although no all mechanisms are understood. Immunoregulatory mechanisms such as apoptosis are important for the control of Chagas disease, possibly affecting the morbidity in chronic clinical forms. Apoptosis has been suggested to be an important mechanism of cellular response during T. cruzi infection. We aimed to further understand the putative role of apoptosis in Chagas disease and its relation to the clinical forms of the disease. Apoptosis of lymphocytes, under antigenic stimuli (soluble T. cruzi antigens - TcAg) where compared to that of non-stimulated cells. Apoptosis was evaluated using the expression of annexin and caspase 3(+) by T cells and the percentage of cells positive evaluated by flow cytometry. In addition activation and T cell markers were used for the identification of TCD4(+) and TCD8(+) subpopulations. The presence of intracellular and plasma cytokines were also evaluated. Analysis of the activation status of the peripheral blood cells showed that patients with Chagas disease presented higher levels of activation determined by the expression of activation markers, after TcAg stimulation. PCR array were used to evaluate the contribution of this mechanism in specific cell populations from patients with different clinical forms of human Chagas disease. Our results showed a reduced proliferative response associated a high expression of T CD4(+)CD62L(-) cells in CARD patients when compared with IND group and NI individuals. We also observed that both groups of patients presented a significant increase of CD4(+) and CD8(+) T cell subsets in undergoing apoptosis after in vitro stimulation with T. cruzi antigens. In CARD patients, both CD4(+) and CD8(+) T cells expressing TNF-α were highly susceptible to undergo apoptosis after in vitro stimulation. Interestingly, the in vitro TcAg stimulation increased considerably the expression of cell death TNF/TNFR superfamily and Caspase family receptors genes in CARD patients. Taken together, our results suggest that apoptosis may be an important mechanism for the control of morbidity in T. cruzi infection by modulating the expression of apoptosis genes, the cytokine environment and/or killing of effector cells.

The effectiveness of natural and synthetic immunomodulators in the treatment of inflammatory bowel disease in dogs.

PubMed

Rychlik, Andrzej; Nieradka, Renata; Kander, Małgorzata; Nowicki, Marcin; Wdowiak, Michał; Kołodziejska-Sawerska, Anna

2013-09-01

The aim of the study was to evaluate the usefulness of immunomodulators in the treatment of inflammatory bowel disease (IBD) in dogs. Twenty-eight dogs diagnosed with IBD took part in the study. The animals received a food containing extruded immunomodulators: β-1,3/1,6-D-glucan, β-hydroxy-β-methyl-butyrate (HMB) and levamisole for 42 days. Whole blood samples were analysed before and after therapy assessing changes in phagocyte activity (respiratory burst activity, RBA and potential killing activity, PKA), evaluation of proliferation response of mitogen-stimulated lymphocytes and serum gamma globulin levels, lysozyme activity, ceruloplasmin levels and interleukin activity (IL-6 and IL-10). In this experiment, β-1,3/1,6-D-glucan delivered the highest level of treatment efficacy by producing the quickest therapeutic effect, lowering Canine Inflammatory Bowel Disease Activity Index (CIBDAI) values to below 3, improving histopathological parameters, decreasing IL-6 levels, increasing IL-10 concentrations, and producing remission periods longer than six months. HMB and levamisole were also effective in lowering CIBDAI scores, but the abatement of clinical symptoms was slower and less pronounced in comparison with β-1,3/1,6-D-glucan. The results indicate that β-1,3/1,6-D-glucan can be useful in the treatment of canine IBD.

Disease Activity Score on 28 Joints and Polypharmacy Are Independent Predictors for Health-Related Quality of Life Evaluated by INCAVISA in Patients With Rheumatoid Arthritis.

PubMed

González-Gamboa, Linda Mariana; Barocio-Ramírez, Ana Karen; Rocha-Muñoz, Alberto Daniel; de Santos-Ávila, Fabiola; Meda-Lara, Rosa M; González-López, Laura; Gámez-Nava, Jorge Iván; Gómez-Bañuelos, Eduardo; Chavarria-Avila, Efrain; Durán-Barragán, Sergio; Navarro-Hernández, Rosa Elena; Pizano-Martínez, Oscar Enrique; Nuñez-Atahualpa, Lourdes; Vázquez-Del Mercado, Mónica

2016-12-01

The aim of this study was to investigate the main factors associated to a diminished health-related quality of life (HRQoL) evaluated by INCAVISA (Health-Related Quality of Life Inventory for Latin American Patients) in patients with rheumatoid arthritis (RA). Female, 18 years or older, RA (American College of Rheumatology 1987 criteria and American College of Rheumatology/European League against Rheumatism 2010 criteria) patients who attended the outpatient rheumatology department of the Hospital Civil "Dr. Juan I. Menchaca," Guadalajara, Mexico, matched with healthy controls were included. Patients with any known comorbidities or treatment with antidepressive drugs were excluded. Trained physicians performed the RA clinical evaluation and INCAVISA. All data were analyzed using SPSS 21.0 software (SPSS Inc, Chicago, IL); P < 0.05 was considered statistically significant. Patients with polypharmacy (≥3 drugs) had a lower HRQoL by INCAVISA. The number of drugs, total comorbidities, and DAS-28 (Disease Activity Score on 28 Joints) were negatively correlated with total INCAVISA. In multivariate analysis, DAS-28 and polypharmacy were independent predictors for a negative perception of HRQoL evaluated by INCAVISA in RA patients. Disease activity and disability secondary to RA have a negative impact in the HRQoL. Other factors such as the number of drugs prescribed to these patients have been shown to be important for the negative perception of their HRQoL evaluated by INCAVISA.

Evaluating peer teaching about chronic disease.

PubMed

Guenther, Sylvia; Shadbolt, Narelle; Roberts, Chris; Clark, Tyler

2014-12-01

The primary care areas of priority (PCAP) activity was developed to engage medical students in learning about chronic disease management in a clinical context from their peers. It is one of several summative assessment tasks that occur during a primary care community term rotation in a graduate-entry medical programme. We evaluated the acceptability and effectiveness of the PCAP activity as a combined teaching, learning and assessment innovation. Evaluation and assessment data from students who rotated through the four community term blocks during the 2011-2012 academic year was analysed using both qualitative and quantitative methods. PCAP peer teaching activity is an effective format for teaching about the management of chronic conditions in the community Analysis indicated that 89 per cent (n = 148/166) of responding students rated the PCAP as satisfactory, good or excellent. The marking rubric contained 11 assessable components, including teaching skills, mastery of clinical knowledge, developing a management plan, disease prevention and health promotion opportunities, identifying patient safety issues, the impact of the clinical presentation on the patient and family, and consideration of health equity factors. Analysis of the assessment scores indicated that the majority of students achieved the specified learning outcomes. The PCAP peer teaching activity was an acceptable and effective format for teaching about the management of chronic conditions in the community, and is adaptable to other teaching contexts. Students enjoyed teaching and being taught by their peers, and assessment results indicated that they developed their clinical knowledge as well as their teaching ability regarding chronic disease management. © 2014 John Wiley & Sons Ltd.

The skin tissue is adversely affected by TNF-alpha blockers in patients with chronic inflammatory arthritis: a 5-year prospective analysis

PubMed Central

Machado, Natalia P.; dos Reis Neto, Edgard Torres; Soares, Maria Roberta M. P.; Freitas, Daniele S.; Porro, Adriana; Ciconelli, Rozana M.; Pinheiro, Marcelo M.

2013-01-01

OBJECTIVE: We evaluated the incidence of and the main risk factors associated with cutaneous adverse events in patients with chronic inflammatory arthritis following anti-TNF-α therapy. METHODS: A total of 257 patients with active arthritis who were taking TNF-α blockers, including 158 patients with rheumatoid arthritis, 87 with ankylosing spondylitis and 12 with psoriatic arthritis, were enrolled in a 5-year prospective analysis. Patients with overlapping or other rheumatic diseases were excluded. Anthropometric, socioeconomic, demographic and clinical data were evaluated, including the Disease Activity Score-28, Bath Ankylosing Spondylitis Disease Activity Index and Psoriasis Area Severity Index. Skin conditions were evaluated by two dermatology experts, and in doubtful cases, skin lesion biopsies were performed. Associations between adverse cutaneous events and clinical, demographic and epidemiological variables were determined using the chi-square test, and logistic regression analyses were performed to identify risk factors. The significance level was set at p<0.05. RESULTS: After 60 months of follow-up, 71 adverse events (73.85/1000 patient-years) were observed, of which allergic and immune-mediated phenomena were the most frequent events, followed by infectious conditions involving bacterial (47.1%), parasitic (23.5%), fungal (20.6%) and viral (8.8%) agents. CONCLUSION: The skin is significantly affected by adverse reactions resulting from the use of TNF-α blockers, and the main risk factors for cutaneous events were advanced age, female sex, a diagnosis of rheumatoid arthritis, disease activity and the use of infliximab. PMID:24141833

The value of power Doppler ultrasound in patients with rheumatoid arthritis in clinical remission: Reclassifying disease activity?

PubMed

Vergara, Facundo; Ruta, Santiago; Rosa, Javier; Marín, Josefina; García-Mónaco, Ricardo; Soriano, Enrique R

2017-03-18

The aim of the present study was to describe the ultrasound (US) findings in patients with rheumatoid arthritis (RA) in clinical remission, and to evaluate the ability of power Doppler (PD) US to reclassify disease activity in these patients. We included consecutive patients with RA according to 2010 American College of Rheumatology/European League Against Rheumatism criteria, who were in clinical remission by the Disease Activity Score (DAS28<2.6). Twenty joints of both hands were assessed by US. PD signal was evaluated on a semi-quantitative scale from 0 to 3. Three different US-modified DAS28 (US-DAS28) were constructed, replacing the clinical swollen joint count by the PD US joint count using PD score ≥1, ≥2 or ≥3, respectively. Eighty-six patients were included. Twenty-three (26.7%) patients had at least one joint with abnormal US-positive PD signal. Thirteen percent of patients were reclassified to low disease activity by applying the US-DAS28 when joints were considered active with a PD signal ≥1; 12%, when a PD signal ≥2 was considered, and 2% of the patients were reclassified when a PD score of 3 was considered. No patients were reclassified to a level of moderate or high activity applying US-DAS28. Although around a quarter of patients with RA in clinical remission showed PD US features indicating residual activity, only a small percentage were reclassified to a state of low activity and none to a level of moderate or high activity, applying the proposed US-DAS28. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

An ex vivo evaluation of the efficacy of andrographolide in modulating differential expression of transcription factors and target genes in periodontal cells and its potential role in treating periodontal diseases.

PubMed

Ambili R; Janam, Prasanthila; Saneesh Babu, P S; Prasad, Manu; Vinod, D; Anil Kumar, P R; Kumary, T V; Asha Nair, S; Radhakrishna Pillai, M

2017-01-20

Andrographolide is a herbal extract traditionally used in South Asian countries for treating inflammatory diseases. To evaluate the efficacy of andrographolide in management of periodontal disease which is a highly prevalent oral disease. Periodontal ligament fibroblasts (PDLF) were cultured from healthy and diseased periodontium using explant culture methods. The safe dose of AG was determined using MTT assay. LPS (lipopolysaccharide) of the most important periodontopathogen, P gingivalis was used to activate NF-κB and STAT3 in PDLF. The efficacy of AG in inhibiting NF-κB and STAT3 was analyzed using immunofluorescence. Down regulation of expression of target genes of these transcription factors related to inflammation and bone resorption were analyzed using real time PCR. AG up to the concentration of 25μM was found to be safe as determined by MTT assay. Statistically significant activation of NF-κB and STAT3 in cultured PDLF was observed in diseased group compared to healthy controls before and after LPS challenge. 5μM AG pretreatment significantly inhibited activation of NF-κB and STAT3 and down regulated expression of inflammatory and bone resorptive genes in cultured PDLF. The findings of the present study propose the adjunctive use of a novel herbal drug andrographolide as a promising host modulation agent for periodontal therapy by inhibiting NF-κB and STAT3 activation and inhibition of inflammation and bone resorption related genes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Improving inflammatory arthritis management through tighter monitoring of patients and the use of innovative electronic tools

PubMed Central

van Riel, Piet; Combe, Bernard; Abdulganieva, Diana; Bousquet, Paola; Courtenay, Molly; Curiale, Cinzia; Gómez-Centeno, Antonio; Haugeberg, Glenn; Leeb, Burkhard; Puolakka, Kari; Ravelli, Angelo; Rintelen, Bernhard; Sarzi-Puttini, Piercarlo

2016-01-01

Treating to target by monitoring disease activity and adjusting therapy to attain remission or low disease activity has been shown to lead to improved outcomes in chronic rheumatic diseases such as rheumatoid arthritis and spondyloarthritis. Patient-reported outcomes, used in conjunction with clinical measures, add an important perspective of disease activity as perceived by the patient. Several validated PROs are available for inflammatory arthritis, and advances in electronic patient monitoring tools are helping patients with chronic diseases to self-monitor and assess their symptoms and health. Frequent patient monitoring could potentially lead to the early identification of disease flares or adverse events, early intervention for patients who may require treatment adaptation, and possibly reduced appointment frequency for those with stable disease. A literature search was conducted to evaluate the potential role of patient self-monitoring and innovative monitoring of tools in optimising disease control in inflammatory arthritis. Experience from the treatment of congestive heart failure, diabetes and hypertension shows improved outcomes with remote electronic self-monitoring by patients. In inflammatory arthritis, electronic self-monitoring has been shown to be feasible in patients despite manual disability and to be acceptable to older patients. Patients' self-assessment of disease activity using such methods correlates well with disease activity assessed by rheumatologists. This review also describes several remote monitoring tools that are being developed and used in inflammatory arthritis, offering the potential to improve disease management and reduce pressure on specialists. PMID:27933206

New 1,2,3-triazole-based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations.

PubMed

Leite, Débora Inácio; Fontes, Fábio de Vasconcellos; Bastos, Monica Macedo; Hoelz, Lucas Villas Boas; Bianco, Maria da Conceição Avelino Dias; de Oliveira, Andressa Paula; da Silva, Patricia Bernardino; da Silva, Cristiane França; Batista, Denise da Gama Jean; da Gama, Aline Nefertiti Silva; Peres, Raiza Brandão; Villar, Jose Daniel Figueroa; Soeiro, Maria de Nazaré Correia; Boechat, Nubia

2018-05-09

Chagas disease has spread throughout the world mainly because of the migration of infected individuals. In Brazil, only benznidazole (Bnz) is used; however, it is toxic and not active in the chronic phase, and cases of resistance are described. This work aimed at the synthesis and the trypanocidal evaluation in vitro and in vivo of six new Bnz analogues (3-8). They were designed by exploring the bioisosteric substitution between the amide group contained in Bnz and the 1,2,3-triazole ring. All the compounds were synthesized in good yields. With the exception of compound 7, the in vitro biological evaluation shows that all Bnz analogues were active against the amastigote form, whereas only compounds 3, 4, 5, and 8 were active against trypomastigote. Compounds 4 and 5 showed the most promising activities in vitro against the form of trypomastigote, being more active than Bnz. In vivo evaluation of compounds, 3-8 showed lower potency and higher toxicity than Bnz. Although the 1,2,3-triazole ring has been described in the literature as an amide bioisostere, its substitution here has reduced the activity of the compounds and made them more toxic. Thus, further molecular optimization could provide novel therapeutic agents for Chagas' disease. © 2018 John Wiley & Sons A/S.

Markers of activated inflammatory cells correlate with severity of liver damage in children with nonalcoholic fatty liver disease.

PubMed

De Vito, Rita; Alisi, Anna; Masotti, Andrea; Ceccarelli, Sara; Panera, Nadia; Citti, Arianna; Salata, Michele; Valenti, Luca; Feldstein, Ariel E; Nobili, Valerio

2012-07-01

Concomitantly to the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of liver disease in children. NAFLD encompasses a spectrum of histological damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), with possible progression to cirrhosis. There is growing evidence that the immune system plays a pivotal role in the initiation and progression to NASH but the cellular nature of the hepatic inflammation is still unknown. The present study includes 34 children with biopsy-proven NAFLD. Liver damage was evaluated by the NAFLD activity score (NAS), and the inflammatory infiltrate was characterized by immunohistochemistry for CD45, CD3 and CD163 which are markers of leukocytes, T cells and activated Kupffer cells/macrophages, respectively. Our results have shown that CD45+ (P<0.0001) and CD163+ (P<0.0001) cells were markedly increased in children with severe histological activity (NAS≥5) compared to children with lower activity (NAS<5), whereas CD3+ cells were significantly lower (P<0.01) in children with severe histological activity. There was a significant association between the numbers of CD45+, CD3+ and CD163+ cells, regarding both the portal tract and liver lobule, and the severity of steatosis, ballooning and fibrosis (P<0.01). These data suggest that the severity and composition of the inflammatory infiltrate correlate with steatosis and the severity of disease in children with NAFLD. Moreover, a decrease in CD3+ cells may be involved in the pathogenesis of liver damage. Future studies should evaluate whether it can predict the progression of liver disease independently of established histological scores.

Antimicrobial Activity of Plant Extracts from Aloe Vera, Citrus Hystrix, Sabah Snake Grass and Zingiber Officinale against Pyricularia Oryzae that causes Rice Blast Disease in Paddy Plants

NASA Astrophysics Data System (ADS)

Uda, M. N. A.; Harzana Shaari, N.; Shamiera. Said, N.; Hulwani Ibrahim, Nur; Akhir, Maisara A. M.; Khairul Rabani Hashim, Mohd; Salimi, M. N.; Nuradibah, M. A.; Hashim, Uda; Gopinath, Subash C. B.

2018-03-01

Rice blast disease, caused by the fungus known as Pyricularia oryzae, has become an important and serious disease of rice worldwide. Around 50% of production may be lost in a field moderately affected by infection and each year the fungus destroys rice, which is enough to feed an estimated 60 million people. Therefore, use of herbal plants offer an alternative for the management of plant diseases. Herbal plant like Aloe vera, Citrus hystrix, Sabah snake grass and Zingiber officinale extracts can be used for controlling disease of rice blast. In this study, these four herbal plants were used for evaluating antimicrobial activity against rice plant fungus Pyricularia oryzae, which causes rice blast disease.

Evaluation of 2-Thioxo-2,3,5,6,7,8-hexahydropyrimido[4,5-d]pyrimidin-4(1H)-one analogues as GAA Activators

PubMed Central

Marugan, Juan J.; Zheng, Wei; Motabar, Omid; Southall, Noel; Goldin, Ehud; Sidransky, Ellen; Aungst, Ronald A.; Liu, Ke; Sadhukhan, Subir Kumar; Austin, Christopher P.

2010-01-01

Pompe disease is a lysosomal storage disease (LSD) caused by a deficiency in the lysosomal enzyme acid α-glucosidase. In several LSDs, enzyme inhibitors have been used as small molecule chaperones to facilitate and increase the translocation of mutant protein from the endoplasmic reticulum to the lysosome. Enzyme activators with chaperone activity would be even more desirable as they would not inhibit the enzyme after translocation and might potentiate the activity of the enzyme that is successfully translocated. Herein we report our initial findings of a new series of acid α-glucosidase activators. PMID:20206419

Evaluation of 2-thioxo-2,3,5,6,7,8-hexahydropyrimido[4,5-d]pyrimidin-4(1H)-one analogues as GAA activators.

PubMed

Marugan, Juan J; Zheng, Wei; Motabar, Omid; Southall, Noel; Goldin, Ehud; Sidransky, Ellen; Aungst, Ronald A; Liu, Ke; Sadhukhan, Subir Kumar; Austin, Christopher P

2010-05-01

Pompe disease is a lysosomal storage disease (LSD) caused by a deficiency in the lysosomal enzyme acid alpha-glucosidase. In several LSDs, enzyme inhibitors have been used as small molecule chaperones to facilitate and increase the translocation of mutant protein from the endoplasmic reticulum to the lysosome. Enzyme activators with chaperone activity would be even more desirable as they would not inhibit the enzyme after translocation and might potentiate the activity of the enzyme that is successfully translocated. Herein we report our initial findings of a new series of acid alpha-glucosidase activators.

Clinical utility of sympathetic blockade in cardiovascular disease management.

PubMed

Park, Chan Soon; Lee, Hae-Young

2017-04-01

A dysregulated sympathetic nervous system is a major factor in the development and progression of cardiovascular disease; thus, understanding the mechanism and function of the sympathetic nervous system and appropriately regulating sympathetic activity to treat various cardiovascular diseases are crucial. Areas covered: This review focused on previous studies in managing hypertension, atrial fibrillation, coronary artery disease, heart failure, and perioperative management with sympathetic blockade. We reviewed both pharmacological and non-pharmacological management. Expert commentary: Chronic sympathetic nervous system activation is related to several cardiovascular diseases mediated by various pathways. Advancement in measuring sympathetic activity makes visualizing noninvasively and evaluating the activation level even in single fibers possible. Evidence suggests that sympathetic blockade still has a role in managing hypertension and controlling the heart rate in atrial fibrillation. For ischemic heart disease, beta-adrenergic receptor antagonists have been considered a milestone drug to control symptoms and prevent long-term adverse effects, although its clinical implication has become less potent in the era of successful revascularization. Owing to pathologic involvement of sympathetic nervous system activation in heart failure progression, sympathetic blockade has proved its value in improving the clinical course of patients with heart failure.

Influence of physiotherapy on severity of motor symptoms and quality of life in patients with Parkinson disease.

PubMed

Cholewa, J; Boczarska-Jedynak, M; Opala, G

2013-01-01

Parkinson disease (PD) is one of the most frequent diseases of the central nervous system. Rehabilitation is one of the factors which may help the patients to maintain higher physical activity in everyday life. The aim of this work was to evaluate the influence of movement rehabilitation on severity of motor symptoms in PD patients. The study included 70 patients suffering from PD according to the Hoehn and Yahr scale. Patients' clinical status was assessed with Unified Parkinson's Disease Rating Scale (UPDRS) parts I-III. Additionally, activity of daily living was evaluated with the Schwab and England scale. The quality of life was evaluated by the Parkinson's Disease Questionnaire (PDQ-39). The examinations were conducted before and after the twelve weeks of the experiment. Patients included in the intervention group (n = 40) took part in 60-minute rehabilitation exercises twice a week, which were aimed at increasing movement ranges, balance improvement, movement agility and walking. The main emphasis was placed on the ability to cope with daily activities. A significant difference in scores of given scales before and after the 12-week period was observed in the intervention group: UPDRS part I score decreased by 17.31%, part II decreased by 22.2%, part III decreased by 18.96%, and PDQ-39 score decreased by 17.12%. Mean score of the Schwab and England scale increased by 9.69%, indicating an improved quality of life. The applied rehabilitation programme decreased the severity of motor symptoms in patients with PD.

Objectively Assessed Physical Activity and its Association with Balance, Physical Function and Dyskinesia in Parkinson's Disease.

PubMed

Nero, Håkan; Benka Wallén, Martin; Franzén, Erika; Conradsson, David; Ståhle, Agneta; Hagströmer, Maria

2016-10-19

The desirable effects of physical activity in individuals with Parkinson's disease are well-known, although according to results from previous studies factors associated with objectively assessed physical activity are not fully investigated. To investigate demographic, disease-related and mobility-related factors that associate with objectively measured physical activity, in a sample of older adults with mild to moderate Parkinson's disease. Demographic, disease-related and mobility-related factors were gathered by interview from a total of 91 older adults with Parkinson's disease, followed by an evaluation of balance control using the Mini-BESTest. After initial testing, participants wore a tri-axial accelerometer during a week of free-living. Correlation analysis and multiple linear regression was used to investigate factors associated with total PA, represented by total activity counts, and time in brisk walking. Motor impairment, physical function, body mass index and dyskinesia contributed to the variance of total physical activity, explaining 34 % of the variance, while physical function and balance control were significant factors associated with brisk walking, explaining 22 %. This study identified factors that have not been shown to associate with objectively measured physical activity previously, such as dyskinesia, balance control and self-rated physical function. The findings also demonstrated that associated factors differ, depending on the activity behavior being investigated. However, other factors than those included in this study may also be of importance.

IL-18 Serum Level in Adult Onset Still's Disease: A Marker of Disease Activity

PubMed Central

Colafrancesco, Serena; Priori, Roberta; Alessandri, Cristiano; Perricone, Carlo; Pendolino, Monica; Picarelli, Giovanna; Valesini, Guido

2012-01-01

Introduction. Immunological factors seem to play a pivotal role in Adult Onset Still's Disease (AOSD). Among all, IL-18 cytokine is overexpressed and drives the inflammatory process. Objective. We aimed to investigate the levels of IL-18 in sera of Italian patients with AOSD and to assess its possible role as a marker of disease activity. Methods. IL-18 serum levels were determined by ELISA in 26 Italian patients with AOSD. Disease activity was assessed using Pouchot's criteria. As controls, 21 patients with Rheumatoid Arthritis (RA), 21 patients with Sjogren's Syndrome (SS), 20 patients with Systemic Lupus Erythematosus (SLE), and 21 healthy subjects (normal human sera, NHS) were evaluated. Results. IL-18 serum levels were significantly higher in patients with active AOSD than in non-active (P = 0.001) and control groups (RA P = 0.0070, SS P = 0.0029, SLE P = 0.0032, NHS P = 0.0004). A significant correlation between IL-18 serum levels and disease activity (P < 0.0001), and laboratory parameters as ferritin (P = 0.0127) and C-reactive protein (P = 0.0032) was demonstrated. Conclusions. Higher levels of IL-18 are detected in active AODS patients and correlate with disease activity and inflammatory laboratory features. ROC-AUC analysis of the serum concentration of IL-18 suggests that it can be considered a diagnostic marker of AOSD. This paper supports the targeting of this cytokine as a possible therapeutic option in AOSD. PMID:22762008

Development of a questionnaire measuring instrumental activities of daily living (IADL) in patients with brain tumors: a pilot study.

PubMed

Oort, Q; Dirven, L; Meijer, W; Sikkes, S A M; Uitdehaag, B M J; Reijneveld, J C; Taphoorn, M J B

2017-03-01

Both dementia and brain tumor patients exhibit cognitive decline during the course of their disease. They might therefore experience similar problems with cognitively complex daily activities (i.e., instrumental activities of daily living (IADL)). The study's objective is to evaluate if the Amsterdam IADL Questionnaire © (A-IADL-Q), a 70-item IADL questionnaire developed for and validated in early dementia patients, is also applicable to glioma patients. The evaluation consisted of three steps. Predetermined decision rules defined which activities were retained, altered, added or excluded. In the first step, 6 neuro-oncology health care professionals (HCP) and 10 glioma patient-proxy dyads were asked to evaluate the 70 A-IADL-Q activities. In the second step, in-depth interviews were conducted with 6 HCPs and 6 other patient-proxy dyads to generate relevant activities specific to glioma patients not covered by the A-IADL-Q. In the third step, 6 new patient-proxy dyads were cognitively debriefed with the list of activities constructed in the previous steps. Results indicated that in step 1, after alterations and exclusions, 28/70 activities could be retained. Nine newly generated activities were subsequently added in step 2. In step 3, the 37 activities were presented to the patient-proxy dyads. Based on their input, several additional alterations and exclusions were made resulting in a list of 32 activities. In conclusion, this evaluation of the A-IADL-Q showed that dementia-specific IADL activities are only partly applicable to glioma patients, and that the addition of glioma specific IADL activities is necessary to capture the IADL construct. This underlines the need for a disease-specific IADL questionnaire for brain tumor patients.

Healthy hearts--and the universal benefits of being physically active: physical activity and health.

PubMed

Blair, Steven N; Morris, Jeremy N

2009-04-01

Although ancient thinkers suggested that physical activity is good for health, systematic research on the topic did not begin until the middle of the 20th century. Early reports showed that individuals in active occupations had lower rates of heart disease than individuals in sedentary occupations. Investigators then began to evaluate leisure-time physical activity and health and found similar results. Later research used objective measures of cardiorespiratory fitness as the exposure, and found even stronger associations with health outcomes. Recent research has extended the earlier findings on activity or fitness and heart disease to a wide variety of health outcomes. We now know that regular physical activity of 150 minutes/week of moderate intensity physical activity reduces the risk of numerous chronic diseases, preserves health and function (both physical and mental) into old age, and extends longevity. The current challenge is to develop programs and interventions to promote physical activity for all in our increasingly sedentary societies.

Anti-nucleosome antibodies as a disease marker in systemic lupus erythematosus and its correlation with disease activity and other autoantibodies.

PubMed

Pradhan, Vandana D; Patwardhan, Manisha M; Ghosh, Kanjaksha

2010-01-01

Detection of anti-nucleosome antibodies (anti-nuc) in patients with systemic lupus erythematosus (SLE) has been well established and it is claimed that their presence is associated with disease activity. The aim of this study is to evaluate the incidence of anti-nuc antibodies and to correlate them with disease activity and its association with other autoantibodies like anti-nuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA), anti-histone antibodies (AHA), as well as autoantibodies to histone subfractions like H1, (H2A-H4) complex, H2B, and H3. This cross-sectional study included 100 SLE patients referred from the Rheumatology, Dermatology, and Nephrology Departments. SLE disease activity was evaluated by using SLE-Disease Activity Index (SLEDAI) score. A patient was defined as having active SLE when the SLEDAI score was more than 5.0. Fifty normal controls were also tested as a healthy control group. Anti-nuc antibodies, anti-dsDNA, and AHA were tested by Enzyme-Linked Immunosorbent Assay (ELISA) and ANA was detected by an indirect immunofluorescence test. All patients studied were in an active stage of disease and were untreated, of which 44 patients had renal biopsy-proven kidney involvement, which was categorized as lupus nephritis (LN) and 56 patients did not show any renal manifestations (SLE without LN). Anti-nuc antibodies were positive in 88%, anti-dsDNA in 80%, and AHA in 38% of the cases. ANA was positive in all SLE patients studied. None of the normal controls was found to be positive for these antibodies. Although a slightly higher incidence of autoantibodies were noted in LN, there was no statistical difference noted between LN and SLE without LN groups for anti-nuc and anti-dsDNA antibodies (p > 0.05). A higher incidence of autoantibodies to ANA specificities were noted in anti-nuc positive cases, but there was no statistical difference between anti-nuc positive and anti-nuc negative cases for ANA specificities among LN and SLE without nephritis groups (p > 0.05). Anti-nuc antibody detection could be a better tool for the diagnosis of SLE. Although there was no significant difference in LN and SLE without LN groups, this study suggests that anti-nuc detection can be useful as an additional disease activity marker to other laboratory tests.

[Heart and sport].

PubMed

Gabus, Vincent; Monney, Pierre

2017-05-24

Physical activity is beneficial for health and the cardiovascular risk profile. However, it can be dangerous in people with cardiac disease that might be asymptomatic. Individuals of all ages and all levels engage in sporting activities. The medical approach is different whether one evaluates a young competitive athlete, a sedentary adult who wants to start a recreational sport or a patient with heart disease who wishes to engage in sport. This article summarizes the various recommendations on the subject.

MULTIMODAL IMAGING OF CHOROIDAL LESIONS IN DISSEMINATED MYCOBACTERIUM CHIMAERA INFECTION AFTER CARDIOTHORACIC SURGERY.

PubMed

Böni, Christian; Al-Sheikh, Mayss; Hasse, Barbara; Eberhard, Roman; Kohler, Philipp; Hasler, Pascal; Erb, Stefan; Hoffmann, Matthias; Barthelmes, Daniel; Zweifel, Sandrine A

2017-12-04

To explore morphologic characteristics of choroidal lesions in patients with disseminated Mycobacterium chimaera infection subsequent to open-heart surgery. Nine patients (18 eyes) with systemic M. chimaera infection were reviewed. Activity of choroidal lesions were evaluated using biomicroscopy, fundus autofluorescence, enhanced depth imaging optical coherence tomography, fluorescein angiography/indocyanine green angiography, and optical coherence tomography angiography. Relationships of choroidal findings to systemic disease activity were sought. All 9 male patients, aged between 49 and 66 years, were diagnosed with endocarditis and/or aortic graft infection. Mean follow-up was 17.6 months. Four patients had only inactive lesions (mild disease). In all five patients (10 eyes) with progressive ocular disease, indocyanine green angiography was superior to other tests for revealing new lesions and active lesions correlated with hyporeflective choroidal areas on enhanced depth imaging optical coherence tomography. One eye with a large choroidal granuloma developed choroidal neovascularization. Optical coherence tomography angiography showed areas with reduced perfusion at the inner choroid. All 5 patients with progressive ocular disease had evidence of systemic disease activity within ±6 weeks' duration. Choroidal manifestation of disseminated M. chimaera infection indicates systemic disease activity. Multimodal imaging is suitable to recognize progressive ocular disease. We propose ophthalmologic screening examinations for patients with M. chimaera infection.

A survey of core and support activities of communicable disease surveillance systems at operating-level CDCs in China.

PubMed

Xiong, Weiyi; Lv, Jun; Li, Liming

2010-11-17

In recent years, problems like insufficient coordination, low efficiency, and heavy working load in national communicable disease surveillance systems in China have been pointed out by many researchers. To strengthen the national communicable disease surveillance systems becomes an immediate concern. Since the World Health Organization has recommended that a structured approach to strengthen national communicable disease surveillance must include an evaluation to existing systems which usually begins with a systematic description, we conducted the first survey for communicable disease surveillance systems in China, in order to understand the situation of core and support surveillance activities at province-level and county-level centers for disease control and prevention (CDCs). A nationwide survey was conducted by mail between May and October 2006 to investigate the implementation of core and support activities of the Notifiable Disease Reporting System (NDRS) and disease-specific surveillance systems in all of the 31 province-level and selected 14 county-level CDCs in Mainland China The comments on the performance of communicable disease surveillance systems were also collected from the directors of CDCs in this survey. The core activities of NDRS such as confirmation, reporting and analysis and some support activities such as supervision and staff training were found sufficient in both province-level and county-level surveyed CDCs, but other support activities including information feedback, equipment and financial support need to be strengthened in most of the investigated CDCs. A total of 47 communicable diseases or syndromes were under surveillance at province level, and 20 diseases or syndromes at county level. The activities among different disease-specific surveillance systems varied widely. Acute flaccid paralysis (AFP), measles and tuberculosis (TB) surveillance systems got relatively high recognition both at province level and county level. China has already established a national communicable disease surveillance framework that combines NDRS and disease-specific surveillance systems. The core and support activities of NDRS were found sufficient, while the implementation of those activities varied among different disease-specific surveillance systems.

Effects of long-term cryopreservation on peripheral blood progenitor cells.

PubMed

Vosganian, Gregory S; Waalen, Jill; Kim, Kevin; Jhatakia, Sejal; Schram, Ethan; Lee, Tracey; Riddell, Dan; Mason, James R

2012-11-01

The long-term stability of cryopreserved peripheral blood progenitor cells is an important issue for patients experiencing disease relapse. However, there is no consensus on how to evaluate the long-term effects of cryopreservation. We describe the effect of cryopreservation on viability and progenitor colony activity from 87 individual samples processed at the Scripps Green Hospital Stem Cell Processing Center (La Jolla, CA, USA). We randomly selected 87 peripheral blood hematopoietic stem cell (PBHSC) samples from 60 patients and evaluated the effect of cryopreservation on sample viability and red and white cell colony activity after < 24 h and 7, 10 and 15 years of cryopreservation. Viability was assayed via trypan blue dye exclusion and activity was measured following 14 days of culture. An age at collection older than 50 years may result in suboptimal activity and viability following long-term cryopreservation, while gender and disease status had no effect. Cryopreservation did not significantly affect white or red cell activity following 10 years of cryopreservation. However, for samples stored longer than 10 years, viability and activity significantly decreased. We noted a positive association between higher pre-cryopreservation %CD34 count and colony activity. Cryopreservation of peripheral blood progenitor cells for up to 10 years results in no loss of clonogenic capacity, as determined by culture activity, although longer durations of storage may affect activity. Until validated methods are developed, cryopreserved grafts should be evaluated based on pre-freeze CD34(+) cell counts as assayed by flow cytometry, and post-thaw sample evaluation should be reserved for patients identified as poor mobilizers.

Active and passive surveillance for communicable diseases in child care facilities, Seattle-King County, Washington.

PubMed

MacDonald, J K; Boase, J; Stewart, L K; Alexander, E R; Solomon, S L; Cordell, R L

1997-12-01

The purpose of this study was to develop and evaluate models for public health surveillance of illnesses among children in out-of-home child care facilities. Between July 1992 and March 1994, 200 Seattle-King County child care facilities participated in active or enhanced passive surveillance, or both. Reporting was based on easily recognized signs, symptoms, and sentinel events. Published criteria were used in evaluating surveillance effectiveness, and notifiable disease reporting of participating and nonparticipating facilities was compared. Neither surveillance model was well accepted by child care providers. Enhanced passive and active surveillance had comparable sensitivity. Reporting delays and the large amount of time needed for data entry led to problems with timeliness, especially in terms of written reporting during active surveillance. Widespread active public health surveillance in child care facilities is not feasible for most local health departments. Improvements in public health surveillance in child care settings will depend on acceptability to providers.

The contribution of clinical and psychosocial factors to fatigue in 182 patients with inflammatory bowel disease: a cross-sectional study.

PubMed

Artom, M; Czuber-Dochan, W; Sturt, J; Murrells, T; Norton, C

2017-02-01

Fatigue is a frequently reported and predominant symptom experienced by patients with inflammatory bowel disease (IBD) and its impact has been associated with poorer quality of life (QoL). The complex interplay between disease-related variables and potentially modifiable psychosocial factors in IBD-fatigue has yet to be unravelled. To evaluate the contribution of clinical, sociodemographic and psychosocial factors to the severity and impact of IBD-fatigue and QoL. In a cross-sectional study, 182 patients with IBD were recruited from three tertiary referral hospitals' out-patient clinics in London. Fatigue was assessed utilising the Inflammatory Bowel Disease-Fatigue Scale (IBD-F), the Multidimensional Fatigue Inventory (MFI); and QoL by the Inflammatory Bowel Disease Questionnaire (IBDQ). Patients completed self-report questionnaires evaluating emotional, cognitive and behavioural factors potentially correlated with fatigue. Sociodemographic data were collected. Disease-related and laboratory data were retrieved from patients' hospital electronic medical records. In hierarchical regression models, disease activity was the only clinical factor consistently associated with severity and impact of fatigue and QoL (P = 0.01). More negative fatigue perceptions were significantly associated with greater IBD-F1 scores (P = 0.01). When controlling for clinical factors (disease activity and anti-TNF therapy), negative perceptions of fatigue, and all-or-nothing and avoidance behaviours explained an additional 41% of the variance in fatigue impact (IBD-F2). Apart from disease activity, emotional and behavioural factors and patients' negative fatigue perceptions may be key factors to be addressed. Further exploration of these factors in longitudinal and intervention studies may help to develop effective models of fatigue management. © 2016 John Wiley & Sons Ltd.

Effects of Tai Chi-based cardiac rehabilitation on aerobic endurance, psychosocial well-being, and cardiovascular risk reduction among patients with coronary heart disease: A systematic review and meta-analysis.

PubMed

Liu, Ting; Chan, Aileen Wk; Liu, Yun Hong; Taylor-Piliae, Ruth E

2018-04-01

Tai Chi is an attractive exercise to improve cardiovascular health. This review aimed to synthesize articles written both in Chinese and in English to evaluate the effects of Tai Chi-based cardiac rehabilitation on aerobic endurance, psychosocial well-being and cardiovascular diseases risk reduction for coronary heart diseases patients. PRISMA guidelines were used to search major health databases to identify randomized controlled trials or non-randomized controlled clinical trials that evaluated Tai Chi intervention compared with active or non-active control groups in coronary heart disease patients. When suitable, data were pooled using a random-effects meta-analysis model. Thirteen studies met the inclusion criteria. Tai Chi groups showed a large and significant improvement in aerobic endurance compared with both active and non-active control interventions (standard mean difference (SMD) 1.12; 95% confidence interval (CI): 0.58-1.66; p <0.001). Tai Chi groups also showed a significantly lower level of anxiety (SMD=9.28; CI: 17.46-1.10; p=0.03) and depression (SMD=9.42; CI: 13.59-5.26; p <0.001), and significantly better quality of life (SMD=0.73; 95% CI: 0.39-1.08; p <0.001) compared with non-active control groups. Significant effects of Tai Chi have been found in improving aerobic endurance and psychosocial well-being among coronary heart disease patients. Tai Chi could be a cost-effective and safe exercise option in cardiac rehabilitation. However, the effect of Tai Chi on cardiovascular disease risk reduction has not been amply investigated among coronary heart disease patients. Caution is also warranted in view of a small number of studies for this meta-analysis and potential heterogeneity in differences in the varied designs of Tai Chi intervention.

Huperzine A for Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

PubMed Central

Yang, Guoyan; Wang, Yuyi; Tian, Jinzhou; Liu, Jian-Ping

2013-01-01

Background Huperzine A is a Chinese herb extract used for Alzheimer’s disease. We conducted this review to evaluate the beneficial and harmful effect of Huperzine A for treatment of Alzheimer’s disease. Methods We searched for randomized clinical trials (RCTs) of Huperzine A for Alzheimer’s disease in PubMed, Cochrane Library, and four major Chinese electronic databases from their inception to June 2013. We performed meta-analyses using RevMan 5.1 software. (Protocol ID: CRD42012003249) Results 20 RCTs including 1823 participants were included. The methodological quality of most included trials had a high risk of bias. Compared with placebo, Huperzine A showed a significant beneficial effect on the improvement of cognitive function as measured by Mini-Mental State Examination (MMSE) at 8 weeks, 12 weeks and 16 weeks, and by Hastgawa Dementia Scale (HDS) and Wechsler Memory Scale (WMS) at 8 weeks and 12 weeks. Activities of daily living favored Huperzine A as measured by Activities of Daily Living Scale (ADL) at 6 weeks, 12 weeks and 16 weeks. One trial found Huperzine A improved global clinical assessment as measured by Clinical Dementia Rating Scale (CDR). One trial demonstrated no significant change in cognitive function as measured by Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and activity of daily living as measured by Alzheimer’s disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) in Huperzine A group. Trials comparing Huperzine A with no treatment, psychotherapy and conventional medicine demonstrated similar findings. No trial evaluated quality of life. No trial reported severe adverse events of Huperzine A. Conclusions Huperzine A appears to have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment in participants with Alzheimer’s disease. However, the findings should be interpreted with caution due to the poor methodological quality of the included trials. PMID:24086396

Patient and Disease Characteristics Associated with Activation for Self-Management in Patients with Diabetes, Chronic Obstructive Pulmonary Disease, Chronic Heart Failure and Chronic Renal Disease: A Cross-Sectional Survey Study

PubMed Central

Bos-Touwen, Irene; Schuurmans, Marieke; Monninkhof, Evelyn M.; Korpershoek, Yvonne; Spruit-Bentvelzen, Lotte; Ertugrul-van der Graaf, Inge; de Wit, Niek; Trappenburg, Jaap

2015-01-01

A substantial proportion of chronic disease patients do not respond to self-management interventions, which suggests that one size interventions do not fit all, demanding more tailored interventions. To compose more individualized strategies, we aim to increase our understanding of characteristics associated with patient activation for self-management and to evaluate whether these are disease-transcending. A cross-sectional survey study was conducted in primary and secondary care in patients with type-2 Diabetes Mellitus (DM-II), Chronic Obstructive Pulmonary Disease (COPD), Chronic Heart Failure (CHF) and Chronic Renal Disease (CRD). Using multiple linear regression analysis, we analyzed associations between self-management activation (13-item Patient Activation Measure; PAM-13) and a wide range of socio-demographic, clinical, and psychosocial determinants. Furthermore, we assessed whether the associations between the determinants and the PAM were disease-transcending by testing whether disease was an effect modifier. In addition, we identified determinants associated with low activation for self-management using logistic regression analysis. We included 1154 patients (53% response rate); 422 DM-II patients, 290 COPD patients, 223 HF patients and 219 CRD patients. Mean age was 69.6±10.9. Multiple linear regression analysis revealed 9 explanatory determinants of activation for self-management: age, BMI, educational level, financial distress, physical health status, depression, illness perception, social support and underlying disease, explaining a variance of 16.3%. All associations, except for social support, were disease transcending. This study explored factors associated with varying levels of activation for self-management. These results are a first step in supporting clinicians and researchers to identify subpopulations of chronic disease patients less likely to be engaged in self-management. Increased scientific efforts are needed to explain the greater part of the factors that contribute to the complex nature of patient activation for self-management. PMID:25950517

[Greater level of physical activity associated with better cognitive function in hemodialysis in end stage renal disease].

PubMed

Stringuetta-Belik, Fernanda; Shiraishi, Flávio Gobbis; Oliveira e Silva, Viviana Rugolo; Barretti, Pasqual; Caramori, Jacqueline Costa Teixeira; Bôas, Paulo José Fortes Villas; Martin, Luis Cuadrado; Franco, Roberto Jorge da Silva

2012-01-01

Patients with chronic kidney disease (CKD) have a lower exercise tolerance and poor functional capacity, carry on a sedentary lifestyle. Another important change found in patients with CKD is cognitive dysfunction. Physical inactivity has been associated with cognitive dysfunction in the general population, but few studies have evaluated this association in CKD. To assess the association between physical activity and cognitive function in patients with CKD on hemodialysis (HD). We evaluated 102 patients undergoing HD. The participants completed the International Physical Activity Questionnaire, which assesses the level of physical activity and the Mini Mental State Examination, used for cognitive screening. Patients were divided into three groups according to their level of physical activity (GI: active/GII: irregularly active/GIII: sedentary). It was applied logistic regression analysis and adopted as outcome variable the presence of cognitive impairment and preserving as independent variables those with a probability of statistical difference between groups of less than 0.1. It was considered statistically significant when p less than 0.05. The groups were similar in age, duration of HD, and smoking. Statistically significant difference regarding race, body mass index, diabetes mellitus, underlying disease and degree of cognitive impairment. Regarding laboratory data, the groups differed in terms of creatinine, glucose, hemoglobin and hematocrit. There was significant association with better physical activity and cognitive function, even adjusting for confounding variables. the highest level of physical activity was associated with better cognitive function in CKD patients undergoing HD.

Developing community-driven quality improvement initiatives to enhance chronic disease care in Indigenous communities in Canada: the FORGE AHEAD program protocol.

PubMed

Naqshbandi Hayward, Mariam; Paquette-Warren, Jann; Harris, Stewart B

2016-07-26

Given the dramatic rise and impact of chronic diseases and gaps in care in Indigenous peoples in Canada, a shift from the dominant episodic and responsive healthcare model most common in First Nations communities to one that places emphasis on proactive prevention and chronic disease management is urgently needed. The Transformation of Indigenous Primary Healthcare Delivery (FORGE AHEAD) Program partners with 11 First Nations communities across six provinces in Canada to develop and evaluate community-driven quality improvement (QI) initiatives to enhance chronic disease care. FORGE AHEAD is a 5-year research program (2013-2017) that utilizes a pre-post mixed-methods observational design rooted in participatory research principles to work with communities in developing culturally relevant innovations and improved access to available services. This intensive program incorporates a series of 10 inter-related and progressive program activities designed to foster community-driven initiatives with type 2 diabetes mellitus as the action disease. Preparatory activities include a national community profile survey, best practice and policy literature review, and readiness tool development. Community-level intervention activities include community and clinical readiness consultations, development of a diabetes registry and surveillance system, and QI activities. With a focus on capacity building, all community-level activities are driven by trained community members who champion QI initiatives in their community. Program wrap-up activities include readiness tool validation, cost-analysis and process evaluation. In collaboration with Health Canada and the Aboriginal Diabetes Initiative, scale-up toolkits will be developed in order to build on lessons-learned, tools and methods, and to fuel sustainability and spread of successful innovations. The outcomes of this research program, its related cost and the subsequent policy recommendations, will have the potential to significantly affect future policy decisions pertaining to chronic disease care in First Nations communities in Canada. Current ClinicalTrial.gov protocol ID NCT02234973 . Date of Registration: July 30, 2014.

Significance of diffusion weighted imaging (DWI) as an improving factor in contrast enhanced magnetic resonance imaging (MRI) enterography in evaluation of patients with Crohn's disease.

PubMed

Imširović, Bilal; Zerem, Enver; Efendić, Alma; Mekić Abazović, Alma; Zerem, Omar; Djedović, Muhamed

2018-08-01

Aim To determine capabilities and potential of contrast enhanced magnetic resonance imaging (MRI) enterography in order to establish the diagnosis and to evaluate severity and activity of intestinal inflammation. Methods Fifty-five patients with suspicion for presence of Crohn's disease were evaluated. All patients underwent contrast enhanced MRI enterography and diffusion weighted imaging (DWI), and subsequently endoscopic examination or surgical treatment. Four parameters were analysed: thickening of the bowel wall, and presence of abscess, fistula and lymphadenopathy. Results Comparing results of DWI and contrast enhanced MRI enterography a significant difference between results given through diffusion and histopathological test was found, e.g. a significant difference between results obtained through diffusion and MRI enterography was found. MRI enterography sensitiveness for bowel wall thickening was 97.7% and specificity 70%, whilst DWI sensitivity for bowel wall thickening was 84% and specificity 100%. The diagnostics of abscess and fistula showed no significant difference between DWI and MRI, while in lymphadenopathy significant difference between contrast enhanced MRI enterography and DWI was found. Conclusion Contrast enhanced MRI enterography in combination with DWI allows for excellent evaluation of disease activity, but also problems or complications following it. The examination can be repeated, controlled, and it can contribute to monitoring of patients with this disease. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

Effect of exclusive enteral nutrition on health-related quality of life for adults with active Crohn's disease.

PubMed

Guo, Zhen; Wu, Rong; Zhu, Weiming; Gong, Jianfeng; Zhang, Wei; Li, Yi; Gu, Lili; Li, Ning; Li, Jieshou

2013-08-01

Exclusive enteral nutrition (EEN) is an effective and safe remission induction treatment for Crohn's disease in adults. Its influence on adults' health-related quality of life remains unknown. The aim of this study was to determine the effect of EEN on health-related quality of life in adults with active Crohn's disease. Patients recruited were treated with a polymeric enteral feed that was taken orally in the daytime and via a self-intubated nasogastric tube at night for 4 weeks. Prospective evaluation of disease activity (Crohn's Disease Activity Index, CDAI) and health-related quality of life (Inflammatory Bowel Disease Questionnaire, IBDQ) were performed at enrollment and after 4 weeks of treatment. Patients' feelings about EEN were also investigated through 2 questions. Thirteen patients were treated with 4-week EEN. They had a significant improvement in total IBDQ score (P < .001) and all IBDQ dimensions: bowel symptoms (P < .001), systemic symptoms (P < .001), social function (P = .003), and emotional status (P < .001), with 11 patients (84.6%) achieving clinical remission after treatment. In addition, 8 patients (61.5%) expressed their willingness to receive this 4-week EEN treatment again to induce remission if the disease relapsed. The IBDQ correlated significantly with the CDAI at 4 weeks. A 4-week treatment of EEN improves health-related quality of life significantly in adults with active Crohn's disease and was acceptable by most patients.

Evaluation of traditional Chinese medicinal plants for anti-MRSA activity with reference to the treatment record of infectious diseases.

PubMed

Zuo, Guo-Ying; Zhang, Xin-Juan; Yang, Cui-Xian; Han, Jun; Wang, Gen-Chun; Bian, Zhong-Qi

2012-03-09

The in vitro antimicrobial activities of 30 Chinese medicinal plants were evaluated with reference to the treatment record of infectious diseases in the Traditional Chinese Medicine (TCM) literature. The plant materials were extracted with 80% ethanol and the extracts were primarily screened against conventional clinical pathogens like Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans by the agar diffusion method. Their inhibition zone diameters (IZDs, mm, 50 mg/mL) ranged from 2,048 by the standard broth microdilution method. The seven extracts from M. yunnanensis, S. sinensis, G. morella, E. daneillii, M. squamulata, S. arborescens and B. hancei were determined as the most active extracts, with MICs of 8-64 μg/mL. The results were in good agreement with their traditional applications in skin and other infections.

Minimizing off-Target Mutagenesis Risks Caused by Programmable Nucleases.

PubMed

Ishida, Kentaro; Gee, Peter; Hotta, Akitsu

2015-10-16

Programmable nucleases, such as zinc finger nucleases (ZFNs), transcription activator like effector nucleases (TALENs), and clustered regularly interspersed short palindromic repeats associated protein-9 (CRISPR-Cas9), hold tremendous potential for applications in the clinical setting to treat genetic diseases or prevent infectious diseases. However, because the accuracy of DNA recognition by these nucleases is not always perfect, off-target mutagenesis may result in undesirable adverse events in treated patients such as cellular toxicity or tumorigenesis. Therefore, designing nucleases and analyzing their activity must be carefully evaluated to minimize off-target mutagenesis. Furthermore, rigorous genomic testing will be important to ensure the integrity of nuclease modified cells. In this review, we provide an overview of available nuclease designing platforms, nuclease engineering approaches to minimize off-target activity, and methods to evaluate both on- and off-target cleavage of CRISPR-Cas9.

HIV Type 1 Disease Progression to AIDS and Death in a Rural Ugandan Cohort Is Primarily Dependent on Viral Load Despite Variable Subtype and T-Cell Immune Activation Levels

PubMed Central

Eller, Michael A.; Opollo, Marc S.; Liu, Michelle; Redd, Andrew D.; Eller, Leigh Anne; Kityo, Cissy; Kayiwa, Joshua; Laeyendecker, Oliver; Wawer, Maria J.; Milazzo, Mark; Kiwanuka, Noah; Gray, Ronald H.; Serwadda, David; Sewankambo, Nelson K.; Quinn, Thomas C.; Michael, Nelson L.; Wabwire-Mangen, Fred; Sandberg, Johan K.; Robb, Merlin L.

2015-01-01

Background. Untreated human immunodeficiency virus type 1 (HIV) infection is associated with persistent immune activation, which is an independent driver of disease progression in European and United States cohorts. In Uganda, HIV-1 subtypes A and D and recombinant AD viruses predominate and exhibit differential rates of disease progression. Methods. HIV-1 seroconverters (n = 156) from rural Uganda were evaluated to assess the effects of T-cell activation, viral load, and viral subtype on disease progression during clinical follow-up. Results. The frequency of activated T cells was increased in HIV-1–infected Ugandans, compared with community matched uninfected individuals, but did not differ significantly between viral subtypes. Higher HIV-1 load, subtype D, older age, and high T-cell activation levels were associated with faster disease progression to AIDS or death. In a multivariate Cox regression analysis, HIV-1 load was the strongest predictor of progression, with subtype also contributing. T-cell activation did not emerge an independent predictor of disease progression from this particular cohort. Conclusions. These findings suggest that the independent contribution of T-cell activation on morbidity and mortality observed in European and North American cohorts may not be directly translated to the HIV epidemic in East Africa. In this setting, HIV-1 load appears to be the primary determinant of disease progression. PMID:25404522

Level of daily physical activity in chronic obstructive pulmonary disease (COPD) patients according to GOLD classification.

PubMed

Rodó-Pin, Anna; Balañá, Ana; Molina, Lluís; Gea, Joaquim; Rodríguez, Diego A

2017-02-09

The Global Initiative for Chronic Obstructive Lung Disease (GOLD guideline) for patients with chronic obstructive pulmonary disease does not adequately reflect the impact of the disease because does not take into account daily physical activity (DPA). Forty eight patients (12 in each GOLD group) were prospectively recruited. DPA was evaluated by accelerometer. Patients were classified into 3 levels of activity (very inactive, sedentary, active). No significant differences in levels of physical activity among GOLD groups (P=.361) were observed. The percentages of very inactive patients were 33% in group A, 42% in group B, 42% in group C and 59% in group D. In addition, high percentage of sedentary patients were observed through 4 groups, in group A (50%), B and C (42%, each), and group D (41%). COPD patients has very low levels of physical activity at all stages of GOLD classification even those defined as low impact (such as GOLD A). Is necessary to detect patients at risk who might benefit from specific interventions. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Design, synthesis and biological evaluation of phthalimide-alkylamine derivatives as balanced multifunctional cholinesterase and monoamine oxidase-B inhibitors for the treatment of Alzheimer's disease.

PubMed

Sang, Zhipei; Wang, Keren; Wang, Huifang; Yu, Lintao; Wang, Huijuan; Ma, Qianwen; Ye, Mengyao; Han, Xue; Liu, Wenmin

2017-11-15

A series of novel phthalimide-alkylamine derivatives were synthesized and evaluated as multi-functions inhibitors for the treatment of Alzheimer's disease (AD). The results showed that compound TM-9 could be regarded as a balanced multi-targets active molecule. It exhibited potent and balanced inhibitory activities against ChE and MAO-B (huAChE, huBuChE, and huMAO-B with IC 50 values of 1.2μM, 3.8μM and 2.6 μM, respectively) with low selectivity. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that TM-9 binds simultaneously to the catalytic active site and peripheral anionic site of AChE. Interestingly, compound TM-9 abided by Lipinski's rule of five. Furthermore, our investigation proved that TM-9 indicated weak cytotoxicity, and it could cross the blood-brain barrier (BBB) in vitro. The results suggest that compound TM-9, an interesting multi-targeted active molecule, offers an attractive starting point for further lead optimization in the drug-discovery process against Alzheimer's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of self-reported physical activity and health promotion behaviors on lung cancer survivorship.

PubMed

Sloan, Jeff A; Cheville, Andrea L; Liu, Heshan; Novotny, Paul J; Wampfler, Jason A; Garces, Yolanda I; Clark, Matthew M; Yang, Ping

2016-04-29

There is some initial evidence that an enhanced physical activity level can improve fquality of life, and possibly survival among patients with lung cancer. The primary aim of this project was to evaluate the impact of physical activity on the quality and quantity of life of lung cancer survivors. Between January 1, 1997, and December 31, 2009, a total of 1466 lung cancer survivors completed a questionnaire with patient-reported outcomes for quality of life (QOL), demographics, disease and clinical characteristics, and a measure of physical activity (Baecke Questionnaire). Chi-square tests compared lung cancer survivors who reported being physically active versus not on a variety of the other covariates. Kaplan-Meier estimates and Cox models evaluated the prognostic importance of physical activity level on Overall Survival (OS). Roughly half of the lung cancer survivors had advanced stage disease at the time of survey. Treatment prevalence rates were 61, 54, and 33 % for surgery, chemotherapy and radiotherapy, respectively. The majority (77 %) of survivors reported themselves as physically active. Physically active survivors reported greater activity across all individual Baecke items. Lung cancer survivor-reported QOL indicated the benefits of physical activity in all domains. Survivors receiving chemotherapy or radiation at the time of questionnaire completion were less likely to be physically active (74 and 73 % respectively). In contrast, 84 % of surgical patients were physically active. Disease recurrence rates were the same for physically active and inactive patients (81 % vs 82 %, p = 0.62). Physically active patients survived an average of 4 more years than those who were not physically active (8.4 years versus 4.4 years respectively, log rank p < 0.0001). Being physically active was related to profound advantages in QOL and survival in a large sample of lung cancer survivors.

Intra-Individual Variability of Physical Activity in Older Adults With and Without Mild Alzheimer's Disease.

PubMed

Watts, Amber; Walters, Ryan W; Hoffman, Lesa; Templin, Jonathan

2016-01-01

Physical activity shows promise for protection against cognitive decline in older adults with and without Alzheimer's disease (AD). To better understand barriers to adoption of physical activity in this population, a clear understanding of daily and weekly activity patterns is needed. Most accelerometry studies report average physical activity over an entire wear period without considering the potential importance of the variability of physical activity. This study evaluated individual differences in the amount and intra-individual variability of physical activity and determined whether these differences could be predicted by AD status, day of wear, age, gender, education, and cardiorespiratory capacity. Physical activity was measured via accelerometry (Actigraph GT3X+) over one week in 86 older adults with and without AD (n = 33 and n = 53, respectively). Mixed-effects location-scale models were estimated to evaluate and predict individual differences in the amount and intra-individual variability of physical activity. Results indicated that compared to controls, participants with AD averaged 21% less activity, but averaged non-significantly greater intra-individual variability. Women and men averaged similar amounts of physical activity, but women were significantly less variable. The amount of physical activity differed significantly across days of wear. Increased cardiorespiratory capacity was associated with greater average amounts of physical activity. Investigation of individual differences in the amount and intra-individual variability of physical activity provided insight into differences by AD status, days of monitor wear, gender, and cardiovascular capacity. All individuals regardless of AD status were equally consistent in their physical activity, which may have been due to a highly sedentary sample and/or the early disease stage of those participants with AD. These results highlight the value of considering individual differences in both the amount and intra-individual variability of physical activity.

SUBCHRONIC PULMONARY PATHOLOGY, IRON-OVERLOAD AND TRANSCRIPTIONAL ACTIVITY AFTER LIBBY AMPHIBOLE EXPOSURE IN RAT MODELS OF CARDIOVASCULAR DISEASE

EPA Science Inventory

Background: Surface-available iron (Fe) is proposed to contribute to asbestos-induced toxicity through the production of reactive oxygen species.Objective: Our goal was to evaluate the hypothesis that rat models of cardiovascular disease with coexistent Fe overload would be incre...

Amyloidosis involving the respiratory system: 5-year's experience of a multi-disciplinary group's activity.

PubMed

Scala, Raffaele; Maccari, Uberto; Madioni, Chiara; Venezia, Duccio; La Magra, Lidia Calogera

2015-01-01

Amyloidosis may involve the respiratory system with different clinical-radiological-functional patterns which are not always easy to be recognized. A good level of knowledge of the disease, an active integration of the pulmonologist within a multidisciplinary setting and a high level of clinical suspicion are necessary for an early diagnosis of respiratory amyloidosis. The aim of this retrospective study was to evaluate the number and the patterns of amyloidosis involving the respiratory system. We searched the cases of amyloidosis among patients attending the multidisciplinary rare and diffuse lung disease outpatients' clinic of Pulmonology Unit of the Hospital of Arezzo from 2007 to 2012. Among the 298 patients evaluated during the study period, we identified three cases of amyloidosis with involvement of the respiratory system, associated or not with other extra-thoracic localizations, whose diagnosis was histo-pathologically confirmed after the pulmonologist, the radiologist, and the pathologist evaluation. Our experience of a multidisciplinary team confirms that intra-thoracic amyloidosis is an uncommon disorder, representing 1.0% of the cases of rare and diffuse lung diseases referred to our center. The diagnosis of the disease is not always easy and quick as the amyloidosis may involve different parts of the respiratory system (airways, pleura, parenchyma). It is therefore recommended to remind this orphan disease in the differential diagnosis of the wide clinical scenarios the pulmonologist may intercept in clinical practice.

Amyloidosis involving the respiratory system: 5-year's experience of a multi-disciplinary group's activity

PubMed Central

Scala, Raffaele; Maccari, Uberto; Madioni, Chiara; Venezia, Duccio; La Magra, Lidia Calogera

2015-01-01

Amyloidosis may involve the respiratory system with different clinical-radiological-functional patterns which are not always easy to be recognized. A good level of knowledge of the disease, an active integration of the pulmonologist within a multidisciplinary setting and a high level of clinical suspicion are necessary for an early diagnosis of respiratory amyloidosis. The aim of this retrospective study was to evaluate the number and the patterns of amyloidosis involving the respiratory system. We searched the cases of amyloidosis among patients attending the multidisciplinary rare and diffuse lung disease outpatients' clinic of Pulmonology Unit of the Hospital of Arezzo from 2007 to 2012. Among the 298 patients evaluated during the study period, we identified three cases of amyloidosis with involvement of the respiratory system, associated or not with other extra-thoracic localizations, whose diagnosis was histo-pathologically confirmed after the pulmonologist, the radiologist, and the pathologist evaluation. Our experience of a multidisciplinary team confirms that intra-thoracic amyloidosis is an uncommon disorder, representing 1.0% of the cases of rare and diffuse lung diseases referred to our center. The diagnosis of the disease is not always easy and quick as the amyloidosis may involve different parts of the respiratory system (airways, pleura, parenchyma). It is therefore recommended to remind this orphan disease in the differential diagnosis of the wide clinical scenarios the pulmonologist may intercept in clinical practice. PMID:26229565

Treatment of Crohn's disease with cannabis: an observational study.

PubMed

Naftali, Timna; Lev, Lihi Bar; Yablecovitch, Doron; Yablekovitz, Doron; Half, Elisabeth; Konikoff, Fred M

2011-08-01

The marijuana plant cannabis is known to have therapeutic effects, including improvement of inflammatory processes. However, no report of patients using cannabis for Crohn's disease (CD) was ever published. To describe the effects of cannabis use in patients suffering from CD. In this retrospective observational study we examined disease activity, use of medication, need for surgery, and hospitalization before and after cannabis use in 30 patients (26 males) with CD. Disease activity was assessed by the Harvey Bradshaw index for Crohn's disease. Of the 30 patients 21 improved significantly after treatment with cannabis. The average Harvey Bradshaw index improved from 14 +/- 6.7 to 7 +/- 4.7 (P < 0.001). The need for other medication was significantly reduced. Fifteen of the patients had 19 surgeries during an average period of 9 years before cannabis use, but only 2 required surgery during an average period of 3 years of cannabis use. This is the first report of cannabis use in Crohn's disease in humans. The results indicate that cannabis may have a positive effect on disease activity, as reflected by reduction in disease activity index and in the need for other drugs and surgery. Prospective placebo-controlled studies are warranted to fully evaluate the efficacy and side effects of cannabis in CD.

M-protein-positive chronic active Epstein-Barr virus infection: features mimicking HIV-1 infection.

PubMed

Imashuku, Shinsaku; Azuma, Naoto; Kanegane, Hirokazu; Kasahara, Yoshihito

2009-09-01

Chronic active Epstein-Barr virus infection (CAEBV) is a unique and fatal lymphoproliferative disease (LPD), which often shows high serum IgG and/or IgE. The significance of such immunoglobulin abnormalities in CAEBV has not been fully evaluated and discussed. In addition, such clinical features mimic HIV-1 infection. We report here a case of CAEBV with M-protein detected which may shed a new light on the pathogenesis of this disease.

Dyskinesia in Parkinson's disease: mechanisms and current non-pharmacological interventions.

PubMed

Heumann, Rolf; Moratalla, Rosario; Herrero, Maria Trinidad; Chakrabarty, Koushik; Drucker-Colín, René; Garcia-Montes, Jose Ruben; Simola, Nicola; Morelli, Micaela

2014-08-01

Dopamine replacement therapy in Parkinson's disease is associated with several unwanted effects, of which dyskinesia is the most disabling. The development of new therapeutic interventions to reduce the impact of dyskinesia in Parkinson's disease is therefore a priority need. This review summarizes the key molecular mechanisms that underlie dyskinesia. The role of dopamine receptors and their associated signaling mechanisms including dopamine-cAMP-regulated neuronal phosphoprotein, extracellular signal-regulated kinase, mammalian target of rapamycin, mitogen and stress-activated kinase-1 and Histone H3 are summarized, along with an evaluation of the role of cannabinoid and nicotinic acetylcholine receptors. The role of synaptic plasticity and animal behavioral results on dyskinesia are also evaluated. The most recent therapeutic advances to treat Parkinson's disease are discussed, with emphasis on the possibilities and limitations of non-pharmacological interventions such as physical activity, deep brain stimulation, transcranial magnetic field stimulation and cell replacement therapy. The review suggests new prospects for the management of Parkinson's disease-associated motor symptoms, especially the development of dyskinesia. This review aims at summarizing the key molecular mechanisms underlying dyskinesia and the most recent therapeutic advances to treat Parkinson's disease with emphasis on non-pharmacological interventions such as physical activity, deep brain stimulation (DBS), transcranial magnetic field stimulation (TMS) and cell replacement therapy. These new interventions are discussed from both the experimental and clinical point of view, describing their current strength and limitations. © 2014 International Society for Neurochemistry.

Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: design and rationale for the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2 degrees P)-TIMI 50 trial.

PubMed

Morrow, David A; Scirica, Benjamin M; Fox, Keith A A; Berman, Gail; Strony, John; Veltri, Enrico; Bonaca, Marc P; Fish, Polly; McCabe, Carolyn H; Braunwald, Eugene

2009-09-01

Thrombin potently activates platelets via interaction with the protease-activated receptor 1. SCH 530348 is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin via antagonism of the protease-activated receptor 1. Because SCH 530348 does not interfere with other pathways for hemostasis, it is possible that SCH 530348 reduces thrombosis with less increase in bleeding than do other potent antiplatelet agents. TRA 2 degrees P-TIMI 50 is a phase III, randomized, double-blind, placebo-controlled, multinational clinical trial designed to evaluate the efficacy and safety of SCH 530348 during long-term treatment of patients with established atherosclerotic disease receiving standard therapy (up to 27,000). Eligible patients with a history of myocardial infarction, ischemic stroke, or peripheral arterial disease are randomized 1:1 to SCH 530348 2.5 mg daily or matched placebo until the end of study. Randomization is stratified by the qualifying disease and planned use of a thienopyridine. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, or urgent coronary revascularization. The major secondary end point is the composite of cardiovascular death, myocardial infarction, or stroke. The evaluation of long-term safety includes bleeding defined by the GUSTO and TIMI criteria. Recruitment began in September 2007. The trial will continue until 2,279 primary end points and 1,400 secondary end points are recorded with expected completion in 36 to 44 months from first enrollment. TRA 2 degrees P-TIMI 50 is evaluating whether a new approach to platelet inhibition via interruption of thrombin-mediated platelet activation reduces major cardiovascular events with a favorable safety profile in patients with established atherosclerosis.

Ultrasound and MRI of nerves for monitoring disease activity and treatment effects in chronic dysimmune neuropathies - Current concepts and future directions.

PubMed

Décard, Bernhard F; Pham, Mirko; Grimm, Alexander

2018-01-01

New imaging modalities like high-resolution-ultrasound (HRUS) and MR-Neurography (MRN) are increasingly used for the evaluation of the peripheral nervous system. The increasing knowledge on morphological changes observed in different neuropathies has led to a better understanding of underlying pathophysiological processes. The diagnosis of acquired chronic dysimmune neuropathies (CDN) like chronic inflammatory demyelinating polyneuropathy (CIDP), Lewis-Sumner Syndrome (LSS) or multifocal motor neuropathy (MMN) can be challenging. The current diagnostic criteria and outcome parameters are mainly based on clinical and electrophysiological parameters. Especially in CDN cases with atypical presentation or during early disease stages, the diagnostic accuracy is low and standardized protocols for the evaluation of disease activity and treatment response are lacking. The establishment of combined diagnostic criteria for CDN including imaging modalities could help to improve the diagnostic accuracy, allow a better differentiation of subtypes and facilitate the follow-up of disease course. The appropriate selection of eligible patients and sensitive monitoring of treatment response is mandatory future in treatment trials. In this article, we briefly summarize the clinical presentations and pathophysiological concepts of different CDN like CIDP, LSS and MMN. Furthermore, this review focuses on the diagnostic value of HRUS/MRN and its potential role for the monitoring of disease activity. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Dynamics of Simian Immunodeficiency Virus SIVmac239 Infection in Pigtail Macaques

PubMed Central

Klatt, Nichole R.; Canary, Lauren A.; Vanderford, Thomas H.; Vinton, Carol L.; Engram, Jessica C.; Dunham, Richard M.; Cronise, Heather E.; Swerczek, Joanna M.; Lafont, Bernard A. P.; Picker, Louis J.; Silvestri, Guido

2012-01-01

Pigtail macaques (PTM) are an excellent model for HIV research; however, the dynamics of simian immunodeficiency virus (SIV) SIVmac239 infection in PTM have not been fully evaluated. We studied nine PTM prior to infection, during acute and chronic SIVmac239 infections, until progression to AIDS. We found PTM manifest clinical AIDS more rapidly than rhesus macaques (RM), as AIDS-defining events occurred at an average of 42.17 weeks after infection in PTM compared to 69.56 weeks in RM (P = 0.0018). However, increased SIV progression was not associated with increased viremia, as both peak and set-point plasma viremias were similar between PTM and RM (P = 0.7953 and P = 0.1006, respectively). Moreover, this increased disease progression was not associated with rapid CD4+ T cell depletion, as CD4+ T cell decline resembled other SIV/human immunodeficiency virus (HIV) models. Since immune activation is the best predictor of disease progression during HIV infection, we analyzed immune activation by turnover of T cells by BrdU decay and Ki67 expression. We found increased levels of turnover prior to SIV infection of PTM compared to that observed with RM, which may contribute to their increased disease progression rate. These data evaluate the kinetics of SIVmac239-induced disease progression and highlight PTM as a model for HIV infection and the importance of immune activation in SIV disease progression. PMID:22090099

Dynamics of simian immunodeficiency virus SIVmac239 infection in pigtail macaques.

PubMed

Klatt, Nichole R; Canary, Lauren A; Vanderford, Thomas H; Vinton, Carol L; Engram, Jessica C; Dunham, Richard M; Cronise, Heather E; Swerczek, Joanna M; Lafont, Bernard A P; Picker, Louis J; Silvestri, Guido; Brenchley, Jason M

2012-01-01

Pigtail macaques (PTM) are an excellent model for HIV research; however, the dynamics of simian immunodeficiency virus (SIV) SIVmac239 infection in PTM have not been fully evaluated. We studied nine PTM prior to infection, during acute and chronic SIVmac239 infections, until progression to AIDS. We found PTM manifest clinical AIDS more rapidly than rhesus macaques (RM), as AIDS-defining events occurred at an average of 42.17 weeks after infection in PTM compared to 69.56 weeks in RM (P = 0.0018). However, increased SIV progression was not associated with increased viremia, as both peak and set-point plasma viremias were similar between PTM and RM (P = 0.7953 and P = 0.1006, respectively). Moreover, this increased disease progression was not associated with rapid CD4(+) T cell depletion, as CD4(+) T cell decline resembled other SIV/human immunodeficiency virus (HIV) models. Since immune activation is the best predictor of disease progression during HIV infection, we analyzed immune activation by turnover of T cells by BrdU decay and Ki67 expression. We found increased levels of turnover prior to SIV infection of PTM compared to that observed with RM, which may contribute to their increased disease progression rate. These data evaluate the kinetics of SIVmac239-induced disease progression and highlight PTM as a model for HIV infection and the importance of immune activation in SIV disease progression.

Associations of the Levels of C4d-bearing Reticulocytes and High-avidity Anti-dsDNA Antibodies with Disease Activity in Systemic Lupus Erythematosus.

PubMed

Mora, Claudia; Medina-Rosas, Jorge; Santos, Ana Maria; Jaimes, Diego A; Arbeláez, Ana M; Romero, Consuelo; Cortes, Annie; Londono, John

2016-09-01

There are no laboratory tools that detect early flares in systemic lupus erythematosus (SLE). Our aim was to validate in our population the previous findings of the association of C4d-bearing reticulocytes (R-C4d) compared to anti-dsDNA antibodies, with disease activity assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG) 2004 scales. All patients who met the 1987 American College of Rheumatology classification criteria and were seen consecutively in 2013 at a specialized SLE care clinic were included. Disease activity was established by the SELENA-SLEDAI and BILAG 2004. Anti-dsDNA and R-C4d were quantified in peripheral blood. Comparisons were made between values of active and inactive patients, and the correlations between the SELENA-SLEDAI and serum levels of anti-dsDNA and R-C4d were measured. Sixty-two patients (83.9% women) were included. A total of 32.3% had active disease according to the SELENA-SLEDAI. There was a significant statistical difference (p = 0.0001) in the distribution of R-C4d between disease activity groups. The correlation coefficient between R-C4d and the SELENA-SLEDAI score was rs = 0.738 (p = 0.0001). R-C4d differed between patients with and without activity in the BILAG 2004 constitutional, mucocutaneous, gastrointestinal, renal, and hematological domains. R-C4d showed a higher correlation with SLE activity measured by the SELENA-SLEDAI and BILAG 2004 than anti-dsDNA did, suggesting a possible involvement in diagnosing disease activity. Prospective studies that confirm these findings and evaluate its involvement in followup are needed.

A Multiinstitutional Phase 2 Trial of Pazopanib Monotherapy in Advanced Anaplastic Thyroid Cancer

PubMed Central

Suman, Vera J.; Menefee, Michael E.; Smallridge, Robert C.; Molina, Julian R.; Maples, William J.; Karlin, Nina J.; Traynor, Anne M.; Kumar, Priya; Goh, Boon Cher; Lim, Wan-Teck; Bossou, Ayoko R.; Isham, Crescent R.; Webster, Kevin P.; Kukla, Andrea K.; Bieber, Carolyn; Burton, Jill K.; Harris, Pamela; Erlichman, Charles

2012-01-01

Context/Objectives: Pazopanib, an inhibitor of kinases including vascular endothelial growth factor receptor, demonstrated impressive activity in progressive metastatic differentiated thyroid cancer, prompting its evaluation in anaplastic thyroid cancer (ATC). Design/Setting/Patients/Interventions/Outcome Measures: Preclinical studies, followed by a multicenter single arm phase 2 trial of continuously administered 800 mg pazopanib daily by mouth (designed to provide 90% chance of detecting a response rate of >20% at the 0.10 significance level when the true response rate is >5%), were undertaken. The primary trial end point was Response Evaluation Criteria in Solid Tumors (RECIST) response. Results: Pazopanib displayed activity in the KTC2 ATC xenograft model, prompting clinical evaluation. Sixteen trial patients were enrolled; 15 were treated: 66.7% were female, median age was 66 yr (range 45–77 yr), and 11 of 15 had progressed through prior systemic therapy. Enrollment was halted, triggered by a stopping rule requiring more than one confirmed RECIST response among the first 14 of 33 potential patients. Four patients required one to two dose reductions; severe toxicities (National Cancer Institute Common Toxicity Criteria-Adverse Events version 3.0 grades >3) were hypertension (13%) and pharyngolaryngeal pain (13%). Treatment was discontinued because of the following: disease progression (12 patients), death due to a possibly treatment-related tumor hemorrhage (one patient), and intolerability (radiation recall tracheitis and uncontrolled hypertension, one patient each). Although transient disease regression was observed in several patients, there were no confirmed RECIST responses. Median time to progression was 62 d; median survival time was 111 d. Two patients are alive with disease 9.9 and 35 months after the registration; 13 died of disease. Conclusions: Despite preclinical in vivo activity in ATC, pazopanib has minimal single-agent clinical activity in advanced ATC. PMID:22774206

A case of reactive arthritis in a Ranger Indoctrination Program (RIP) student.

PubMed

Hart, Robert S; Detro, John F

2009-01-01

Musculoskeletal complaints comprise the majority of cases encountered by military physicians when evaluating young active duty Soldier-athletes. This is a case of reactive arthritis in a 19-year-old active duty Soldier-athlete whose failure to improve with conservative therapy initiated further investigation. When evaluating what appear to be routine overuse injuries, it is important to actively include other potential causes of musculoskeletal complaints in the differential diagnosis. Further investigation of disease in patients whose symptoms and complaints do not improve with routine conservative care is paramount. Reactive arthritis, though self-limiting in two-thirds of those affected, can become a chronic disabling disease affecting as many as 40 out of 100 patients. Current theories suggest the persistent presence of non-culturable bacteria and bacterial antigens residing in the joint synovia as the etiology of the disease state. There is no curative therapy for reactive arthritis and management is focused on the treatment of symptoms with non-steroidal anti-inflammatory drugs (NSAIDs), immunomodulator therapy, and antibiotics if an infectious source is suspected.

Immunotherapy for Alzheimer's disease: DNA- and protein-based epitope vaccines.

PubMed

Davtyan, Hayk; Petrushina, Irina; Ghochikyan, Anahit

2014-01-01

Active immunotherapy for Alzheimer's disease (AD) is aimed to induce antibodies specific to amyloid-beta (Aβ) that are capable to reduce the level of Aβ in the CNS of Alzheimer's disease patients. First clinical trial AN-1792 that was based on vaccination with full-length Aβ42 showed that safe and effective AD vaccine should induce high titers of anti-Aβ antibodies without activation of harmful autoreactive T cells. Replacement of self-T cell epitope with foreign epitope, keeping self-B cell epitope intact, may allow to induce high titers of anti-Aβ antibodies while avoiding the activation of T cells specific to Aβ. Here we describe the protocols for evaluation of AD DNA- or multiple antigenic peptide (MAP)-based epitope vaccines composed of Aβ(1-11) B cell epitope fused to synthetic T cell epitope PADRE (Aβ(1-11)-PADRE). All protocols could be used for testing any epitope vaccine constructed in your lab and composed of other T cell epitopes using the appropriate peptides in tests for evaluation of humoral and cellular immune responses.

Outcomes after rheumatoid arthritis patients complete their participation in a long-term observational study with tofacitinib combined with methotrexate: practical and ethical implications in vulnerable populations after tofacitinib discontinuation.

PubMed

Pérez-Román, Diana I; Ortiz-Haro, Ana B; Ruiz-Medrano, Emmanuel; Contreras-Yáñez, Irazú; Pascual-Ramos, Virginia

2018-04-01

To describe disease activity and disability during the first year of follow-up, from rheumatoid arthritis (RA) patients who discontinue tofacitinib after they end participation in a clinical trial. From 2008 to 2016, 36 patients were enrolled in the "Long term follow-up study with tofacitinib (and methotrexate) for RA treatment". At the end of the study, tofacitinib was discontinued and patients were proposed to enter an observational study; 35 agree and had scheduled evaluations at baseline, at 15 and 30 days of follow-up, at month 2 and 3, and thereafter every 3 months. Disease activity was evaluated as per DAS28-ESR and disability as per HAQ. During follow-up, treatment was treat-to-target oriented, only conventional DMARDs were indicated. Descriptive statistics and nonparametric test were used. The study was approved by IRB. Patients were primarily females (N = 34), had median (Q25-75) age of 52 years (45-58), and had received tofacitinib for a median of 7.9 years (6.3-8.3). The proportion of patients with remission and low disease activity decreased from day 30 of follow-up and recovered after 270 days, meanwhile patients with high disease activity increased from 0% at baseline to 6.3% at 1 year. At study entry, 20 patients had remission/low disease activity; during follow-up, 85% deteriorated after (median) 30 days; among them, 23.5% recovered their baseline status after a median of 172.5 days. The HAQ showed a similar behavior, but 66.7% recovered. A substantial proportion of RA patients deteriorated outcomes early after tofacitinib cessation; some patients recovered baseline status with traditional DMARDS.

Serum human chorionic gonadotropin levels and thyroid hormone levels in gestational transient thyrotoxicosis: Is the serum hCG level useful for differentiating between active Graves' disease and GTT?

PubMed

Yoshihara, Ai; Noh, Jaeduk Yoshimura; Mukasa, Koji; Suzuki, Miho; Ohye, Hidemi; Matsumoto, Masako; Kunii, Yo; Watanabe, Natsuko; Suzuki, Nami; Kameda, Toshiaki; Sugino, Kiminori; Ito, Koichi

2015-01-01

Gestational transient thyrotoxicosis (GTT) is defined as transient thyrotoxicosis caused by the stimulating effect of human chorionic gonadotropin (hCG) during pregnancy. We attempted to identify the serum hCG level that causes GTT, and we compared the serum hCG levels and thyroid hormone levels of GTT patients according to whether they had a background of thyroid disease. We also evaluated serum hCG as a parameter for differentiating between active Graves' disease (GD) and GTT. We reviewed the 135 cases of pregnant women who came to our hospital to be evaluated for thyrotoxicosis during their 7th to 14th week of pregnancy, and their serum hCG level was measured at that time. Among the 135 pregnant women with thyrotoxicosis; 103 of the women had GTT, and the other 32 women had active GD. There were no correlations between their serum hCG levels and free thyroid hormone levels. There were no significant differences in thyroid hormone levels or hCG levels among the GTT groups with different thyroid disease backgrounds; i.e., the GTT group without thyroid disease, GTT group with chronic thyroiditis, GTT group with non-functioning thyroid nodules, and GTT group with GD in remission. The serum hCG level of the GTT group was significantly higher than in the active GD group, but it was not a good parameter for differentiating between the two groups. The FT3/FT4 ratio of the active GD was significantly higher than in GTT group, and was a better parameter for differentiation.

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.

Changes in Novel Biomarkers of Disease Activity in Juvenile and Adult Dermatomyositis are Sensitive Biomarkers of Disease Course

PubMed Central

Reed, Ann M.; Peterson, Erik; Bilgic, Hatice; Ytterberg, Steven R.; Amin, Shreyasee; Hein, Molly S.; Crowson, Cynthia S.; Ernste, Floranne; Gillespie, Emily Baechler

2012-01-01

Objective Muscle enzyme levels are insensitive markers of disease activity in juvenile and adult dermatomyositis (DM), especially during the active treatment phase. To improve our ability to monitor DM disease activity longitudinally, especially in the presence of immune modulating agents, we prospectively evaluated whether IFN-dependent peripheral blood gene and chemokine signatures could serve as sensitive and responsive biomarkers for change in disease activity in adult and juvenile DM. Methods Peripheral blood and clinical data were collected from 51 juvenile and adult DM subjects prospectively over 2 study visits. Disease activity measures, whole-blood type I IFN gene and chemokine score were collected. We also measured serum levels of other pro-inflammatory cytokines, including IL-6. Results Changes in juvenile and adult DM global disease activity correlated positively and significantly with changes in the type I IFN gene score before (r=0.33, p=0.023) and IFN chemokine score before and after adjustment for medication use (r=0.53, p<0.001 and r=0.50, p=<0.001). Changes in muscle and extramuscular VAS subscales positively correlated with change in IFN gene and chemokine score (p=0.002). Serum levels of IL-6, IL-8 and TNFα were positively correlated with changes in global, muscle and extra-muscular VAS before and after adjustment for medications (p<0.05). Conclusion Our findings suggest that changes in type I IFN gene and chemokine scores as well as levels of IL-6, IL-8 and TNFα may serve as sensitive and responsive longitudinal biomarkers of change in disease activity in juvenile and adult DM, even in the presence of immunosuppressant use. PMID:22886447

Anti-ulcer activity of leguminosae plants.

PubMed

Paguigan, Noemi D; Castillo, Darryl Hannah B; Chichioco-Hernandez, Christine L

2014-01-01

Ulcer is the most common gastrointestinal disturbance resulting from an inadequate gastric mucosal defense. Several drugs are available in the market to address the disease; however, these drugs are associated with unnecessary side effects. Previous research have confirmed the efficacy of plant extracts for possible treatment of the disease. This research aims to evaluate the anti-ulcer properties of medicinal plants. Methanol extracts from the leaves of Intsia bijuga, Cynometra ramiflora, Tamarindus indica, Cassia javanica, Cassia fistula, Bauhini purpurea, Senna spectabilis, Senna siamea and Saraca thaipingensis were evaluated for their anti-ulcer activity using HCl-ethanol as ulcerogen. All extracts showed inhibitory activity with I. bijuga, T. indica, S. spectabilis and S. thaipingensis exhibiting more than 50% inhibition. S. thaipingensis showed the highest activity at 80%. S. spectabilis and S. thaipingensis were partitioned further into hexane, ethyl acetate and aqueous fractions. The aqueous and ethyl acetate fractions of S. spectabilis showed significant increased in its activity while the hexane and ethyl acetate fractions of S. thaipingensis gave higher activity than its aqueous portions. We conclude that plant extracts are potential sources of new anti-ulcer agents.

Two-year efficacy of tocilizumab in patients with active rheumatoid arthritis in clinical practice.

PubMed

Notario Ferreira, Irene; Ferrer González, Miguel Angel; Morales Garrido, Pilar; González Utrilla, Alfonso; García Sanchez, Antonio; Soto Pino, María José; Suero Rosario, Evelyn; Caro Hernández, Cristina; Añón Oñate, Isabel; Pérez Albaladejo, Lorena; Cáliz Cáliz, Rafael

To evaluate the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, retention rates of the drug and predictors of response. We performed a descriptive, prospective, longitudinal, open-label study in patients receiving TCZ (8mg/kg/4 weeks) in a clinical practice setting. The clinical responses were evaluated using the European League Against Rheumatism (EULAR) response criteria, and the low activity and remission rates according to the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and the Clinical Disease Activity Index (CDAI). The EULAR response rate was 86.63% and the DAS28 remission rate was 53.7% after 6 months of treatment; rates of low disease activity were 52.9% on CDAI and 47.1% on DAS28 at month 24. There were no statistically significant differences in EULAR response, rates of low activity and remission on DAS28 between patients receiving TCZ alone and those receiving TCZ in combination therapy, or between patients positive or negative for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies. The naïve biological therapy patients showed better remission and low activity rates after 6 months of treatment. The retention rate was 61% at month 24. Adverse events were among the most frequent causes of discontinuation. Tocilizumab is effective in RA, has a similar efficacy when used alone or in combination with synthetic disease-modifying antirheumatic drugs (DMARDs) and shows high retention rates. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Initial evaluation of an ultrasound measure for assessing the activity of skin lesions in juvenile localized scleroderma.

PubMed

Li, S C; Liebling, M S; Haines, K A; Weiss, J E; Prann, A

2011-05-01

To evaluate the construct validity of 2 proposed measures (the Ultrasound Disease Activity [U-DA] and the Tissue Thickness Score [TTS]) for evaluating sonographic differences in juvenile localized scleroderma skin lesions. We conducted a retrospective review of juvenile localized scleroderma patients who had ultrasound scans of their skin lesions between October 2005 and February 2009. Imaged lesions were classified as active or inactive based upon clinical assessment. Lesions had to have been imaged within 1 month of a clinic visit or have the same clinical assessment during both the visit before and the visit after the scan. Two physicians scored the scans using the U-DA, which scores for differences in lesion echogenicity and vascularity compared with normal tissue. Tissue thickness differences were evaluated by percent differences and by using the TTS. Wilcoxon's rank sum test was performed to assess differences. We studied 52 scans from 21 patients, 32 scans of active skin lesions and 20 scans of inactive skin lesions. Features reported by clinicians as indicative of active disease included erythema, warmth, violaceous color, new lesion, expansion of lesion, and induration. The U-DA was significantly different between active and inactive skin lesions (P = 0.0010) with significant differences found for the parameters of total echogenicity, hypodermis echogenicity, and deep tissue layer vascularity (P = 0.0014, P = 0.0023, and P = 0.0374, respectively). No significant differences were found for tissue layer thickness or TTS. The U-DA may be a useful tool in the identification of localized scleroderma activity. Further study is needed to prospectively evaluate the validity, reliability, and sensitivity of this potential monitoring tool. Copyright © 2011 by the American College of Rheumatology.

A Practical Green Synthesis and Biological Evaluation of Benzimidazoles Against Two Neglected Tropical Diseases: Chagas and Leishmaniasis.

PubMed

Bandyopadhyay, Debashis; Samano, Selina; Villalobos-Rocha, Juan Carlos; Sanchez-Torres, Luvia Enid; Nogueda-Torres, Benjamin; Rivera, Gildardo; Banik, Bimal K

2017-01-01

Antimicrobial resistance is an ever-increasing problem throughout the world and has already reached severe proportions. Two very common neglected tropical diseases are Chagas' disease and leishmaniasis. Chagas' disease is a severe health problem, mainly in Latin America, causing approximately 50000 deaths a year and millions of people are infected. About 25-30% of the patients infected with Trypanosoma cruzi develop the chronic form of the disease. On the other hand, Leishmaniasis represents complex diseases with an important clinical and epidemiological diversity. It is endemic in 88 countries 72 of which are developing countries and it has been estimated that are 12 million people infected and 350 million are in areas with infection risk. On this basis, research on organic compounds that can be used against these two diseases is an important target. A very simple, green, and efficient protocol is developed in which bismuth nitrate pentahydrate is employed as a Lewis acid catalyst in aqueous media under microwave irradiation for the synthesis of various 2-aryl substituted benzimidazoles from aldehydes and o-phenylenediamine. Other salient features of this protocol include milder conditions, atom-economy, easy extraction, and no wastes. Nine 1H-benzimidazole derivatives (1-9) with substituents at positions 2 and 5 were synthesized and the structure of the compounds was elucidated by spectroscopic methods. The compounds were screened to identify whether they posses pharmacological activity against Chagas' disease and leishmaniasis. Compound 8 showed better activity than the control Nifurtimox against INC-5 Trypanosoma cruzi strain whereas compounds 3 and 9 have demonstrated potent leshmanicidal activity. A systematic green synthetic procedure and in vitro biological evaluation of nine 1H-benzimidazoles are described. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Using ontology-based annotation to profile disease research

PubMed Central

Coulet, Adrien; LePendu, Paea; Shah, Nigam H

2012-01-01

Background Profiling the allocation and trend of research activity is of interest to funding agencies, administrators, and researchers. However, the lack of a common classification system hinders the comprehensive and systematic profiling of research activities. This study introduces ontology-based annotation as a method to overcome this difficulty. Analyzing over a decade of funding data and publication data, the trends of disease research are profiled across topics, across institutions, and over time. Results This study introduces and explores the notions of research sponsorship and allocation and shows that leaders of research activity can be identified within specific disease areas of interest, such as those with high mortality or high sponsorship. The funding profiles of disease topics readily cluster themselves in agreement with the ontology hierarchy and closely mirror the funding agency priorities. Finally, four temporal trends are identified among research topics. Conclusions This work utilizes disease ontology (DO)-based annotation to profile effectively the landscape of biomedical research activity. By using DO in this manner a use-case driven mechanism is also proposed to evaluate the utility of classification hierarchies. PMID:22494789

Responsiveness of Endoscopic Indices of Disease Activity for Crohn's Disease.

PubMed

Khanna, Reena; Zou, GuangYong; Stitt, Larry; Feagan, Brian G; Sandborn, William J; Rutgeerts, Paul; McDonald, John W D; Dubcenco, Elena; Fogel, Ronald; Panaccione, Remo; Jairath, Vipul; Nelson, Sigrid; Shackelton, Lisa M; Huang, Bidan; Zhou, Qian; Robinson, Anne M; Levesque, Barrett G; D'Haens, Geert

2017-10-01

The Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for Crohn's Disease (SES-CD) are commonly used to assess Crohn's disease (CD) activity; however neither instrument is fully validated. We evaluated the responsiveness to change of the SES-CD and CDEIS using data from a trial of adalimumab, a drug therapy of known efficacy. Paired video recordings (N=112) of colonoscopies (baseline and week 8-12) obtained from patients with CD who participated in a trial of adalimumab therapy were reviewed in random order, in duplicate, by four central readers (56 pairs of videos by 2 groups of readers). Responsiveness of the SES-CD and the CDEIS was evaluated by comparing correlations between the observed and pre-specified predictions of change scores for these endoscopic indices with a global endoscopic evaluation of severity (GELS), a patient reported outcome (PRO2), and the Crohn's disease activity index (CDAI), and by calculation of the standardized effect size, and Guyatt's Responsiveness statistic (GRS) using 2 definitions of change; (1) treatment assignment and (2) an absolute change in total PRO2 of 50. The potential application of effect size estimates was demonstrated by calculating hypothetical sample sizes for comparing two independent groups. The impact of removing stenosis as an index item and adjusting for the number of segments observed was also assessed. Changes in both endoscopic instruments and the GELS were highly correlated. The SES-CD displayed numerically higher effect sizes for both definitions of change. The standardized effect size and GRS estimates (95% confidence interval) for the SES-CD based on treatment assignment were 0.84 (0.53, 1.15) and 0.79 (0.48, 1.09). Corresponding values for the CDEIS were 0.72 (0.42, 1.02) and 0.75 (0.45, 1.06). The standardized effect size and GRS estimates for the SES-CD based on an absolute change in total PRO2 of 50 points or greater were 0.76 (0.49, 1.02) and 0.93 (0.64, 1.21). Corresponding values for CDEIS were 0.70 (0.44, 0.97), 0.83 (0.55, 1.10). Removal of stenosis as an index item and adjusting for observed segments did not improve responsiveness estimates. Although both the SES-CD and CDEIS are valid measures of endoscopic disease activity that are moderately responsive to changes in endoscopic disease activity, the SES-CD displayed numerically greater responsiveness in this data set.

Clinical value of gallium-67 scintigraphy in assessment of disease activity in Wegener's granulomatosis

PubMed Central

Slart, R; Jager, P; Poot, L; Piers, D; Cohen, T; Stegeman, C

2003-01-01

Background: Diagnosis of active pulmonary and paranasal involvement in patients with Wegener's granulomatosis (WG) can be difficult. The diagnostic value of gallium-67 scintigraphy in WG is unclear. Objective: To evaluate the added diagnostic value of gallium-67 scintigraphy in patients with WG with suspected granulomatous inflammation in the paranasal and chest regions. Methods: Retrospectively, the diagnostic contribution of chest and head planar gallium scans in 40 episodes of suspected vasculitis disease activity in 28 patients with WG was evaluated. Scans were grouped into normal or increased uptake for each region. Histological proof or response to treatment was the "gold standard" for the presence of WG activity. Results: WG activity was confirmed in 8 (20%) episodes, with pulmonary locations in three, paranasal in four, and both in one (n=7 patients); all these gallium scans showed increased gallium uptake (sensitivity 100%). Gallium scans were negative for the pulmonary area in 23/36 scans (specificity 64%), and negative for paranasal activity in 13/16 scans (specificity 81%) in episodes without WG activity. Positive predictive value of WG activity for lungs and paranasal region was 24% and 63%, respectively, negative predictive value was 100% for both regions. False positive findings were caused by bacterial or viral infections. Conclusion: Gallium scans are clinically helpful as a negative scan virtually excludes active WG. Gallium scintigraphy of chest and nasal region has a high sensitivity for the detection of disease activity in WG. However, because of positive scans in cases of bacterial or viral infections, specificity was lower. PMID:12810430

Comparison of golimumab 100-mg monotherapy to golimumab 50 mg plus methotrexate in patients with rheumatoid arthritis: Results from a multicenter, cohort study.

PubMed

Yonemoto, Yukio; Okamura, Koichi; Takeuchi, Kimihiko; Ayabe, Keio; Kaneko, Tetsuya; Matsushita, Masatoshi; Tamura, Yasuyuki; Iso, Takenobu; Okura, Chisa; Otsuka, Keiko; Inoue, Hiroshi; Takagishi, Kenji

2016-01-01

The aim of this study was to compare the efficacy and safety of golimumab (GLM) 50 mg + methotrexate (MTX) combination therapy and GLM 100 mg monotherapy in patients with rheumatoid arthritis (RA). The subjects were 115 RA patients (92 females and 23 males; median (range) age, 64 (17-87) years; median (range) disease duration, 8 (0.6-48) years) started on GLM. Eighty-three patients received GLM 50 mg/4 weeks + MTX (C group; median (range) MTX dosage 8 (2-16) mg/week), and 32 patients received GLM 100 mg/4 weeks (M group). Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), matrix metalloproteinase-3, disease activity score (DAS) 28-ESR, DAS28-CRP, simplified disease activity index, and clinical disease activity index were evaluated 4, 12, and 24 weeks after starting GLM. There were no significant differences in disease activity, adverse events, and drug continuation rates at 24 weeks between the groups. The DAS28-ESR remission rate was 34% in the C group and 26% in the M group. GLM 100 mg monotherapy improved disease activity as well as GLM 50 mg + MTX combination therapy. GLM 100 mg monotherapy appears to have a sufficient therapeutic effect in RA patients who cannot take MTX.

Blood-based biomarkers used to predict disease activity in Crohn's disease and ulcerative colitis.

PubMed

Burakoff, Robert; Pabby, Vikas; Onyewadume, Louisa; Odze, Robert; Adackapara, Cheryl; Wang, Wei; Friedman, Sonia; Hamilton, Matthew; Korzenik, Joshua; Levine, Jonathan; Makrauer, Frederick; Cheng, Changming; Smith, Hai Choo; Liew, Choong-Chin; Chao, Samuel

2015-05-01

Identifying specific genes that are differentially expressed during inflammatory bowel disease flares may help stratify disease activity. The aim of this study was to identify panels of genes to be able to distinguish disease activity in Crohn's disease (CD) and ulcerative colitis (UC). Patients were grouped into categories based on disease and severity determined by histological grading. Whole blood was collected by PAXgene Blood RNA collection tubes, (PreAnalytiX) and gene expression analysis using messenger RNA was conducted. Logistic regression was performed on multiple combinations of common probe sets, and data were evaluated in terms of discrimination by computing the area under the receiving operator characteristic curve (ROC-AUC). Nine inactive CD, 8 mild CD, 10 moderate-to-severe CD, 9 inactive UC, 8 mild UC, 10 moderate-to-severe UC, and 120 controls were hybridized to Affymetrix U133 Plus 2 microarrays. Panels of 6 individual genes discriminated the stages of disease activity: CD with mild severity {ROC-AUC, 0.89 (95% confidence interval [CI], 0.84%-0.95%)}, CD with moderate-to-severe severity (ROC-AUC 0.98 [95% CI, 0.97-1.0]), UC with mild severity (ROC-AUC 0.92 [95% CI, 0.87-0.96]), and UC with moderate-to-severe severity (ROC-AUC 0.99 [95% CI, 0.97-1.0]). Validation by real-time reverse transcription-PCR confirmed the Affymetrix microarray data. The specific whole blood gene panels reliably distinguished CD and UC and determined the activity of disease, with high sensitivity and specificity in our cohorts of patients. This simple serological test has the potential to become a biomarker to determine the activity of disease.

42 CFR 85.3 - Procedures for requesting health hazard evaluations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES REQUESTS FOR HEALTH HAZARD EVALUATIONS § 85.3..., and Field Studies, NIOSH, 4676 Columbia Parkway, Cincinnati, OH 45226. (2) Requests from mining industry. Environmental Investigations Branch, Division of Respiratory Disease Studies, NIOSH, 944 Chestnut...

42 CFR 85.3 - Procedures for requesting health hazard evaluations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES REQUESTS FOR HEALTH HAZARD EVALUATIONS § 85.3..., and Field Studies, NIOSH, 4676 Columbia Parkway, Cincinnati, OH 45226. (2) Requests from mining industry. Environmental Investigations Branch, Division of Respiratory Disease Studies, NIOSH, 944 Chestnut...

42 CFR 85.3 - Procedures for requesting health hazard evaluations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES REQUESTS FOR HEALTH HAZARD EVALUATIONS § 85.3..., and Field Studies, NIOSH, 4676 Columbia Parkway, Cincinnati, OH 45226. (2) Requests from mining industry. Environmental Investigations Branch, Division of Respiratory Disease Studies, NIOSH, 944 Chestnut...

42 CFR 85.3 - Procedures for requesting health hazard evaluations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES REQUESTS FOR HEALTH HAZARD EVALUATIONS § 85.3..., and Field Studies, NIOSH, 4676 Columbia Parkway, Cincinnati, OH 45226. (2) Requests from mining industry. Environmental Investigations Branch, Division of Respiratory Disease Studies, NIOSH, 944 Chestnut...

42 CFR 85.3 - Procedures for requesting health hazard evaluations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES REQUESTS FOR HEALTH HAZARD EVALUATIONS § 85.3..., and Field Studies, NIOSH, 4676 Columbia Parkway, Cincinnati, OH 45226. (2) Requests from mining industry. Environmental Investigations Branch, Division of Respiratory Disease Studies, NIOSH, 944 Chestnut...

Role of capsule endoscopy in inflammatory bowel disease.

PubMed

Kopylov, Uri; Seidman, Ernest G

2014-02-07

Videocapsule endoscopy (VCE) has revolutionized our ability to visualize the small bowel mucosa. This modality is a valuable tool for the diagnosis of obscure small bowel Crohn's disease (CD), and can also be used for monitoring of disease activity in patients with established small-bowel CD, detection of complications such as obscure bleeding and neoplasms, evaluation of response to anti-inflammatory treatment and postoperative recurrence following small bowel resection. VCE could also be an important tool in the management of patients with unclassified inflammatory bowel disease, potentially resulting in reclassification of these patients as having CD. Reports on postoperative monitoring and evaluation of patients with ileal pouch-anal anastomosis who have developed pouchitis have recenty been published. Monitoring of colonic inflammatory activity in patients with ulcerative colitis using the recently developed colonic capsule has also been reported. Capsule endoscopy is associated with an excellent safety profile. Although retention risk is increased in patients with small bowel CD, this risk can be significanty decreased by a routine utilization of a dissolvable patency capsule preceding the ingestion of the diagnostic capsule. This paper contains an overview of the current and future clinical applications of capsule endoscopy in inflammatory bowel disease.

Ultrasound disease activity of bilateral wrist and finger joints at three months reflects the clinical response at six months of patients with rheumatoid arthritis treated with biologic disease-modifying anti-rheumatic drugs.

PubMed

Kawashiri, Shin-Ya; Nishino, Ayako; Shimizu, Toshimasa; Umeda, Masataka; Fukui, Shoichi; Nakashima, Yoshikazu; Suzuki, Takahisa; Koga, Tomohiro; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Aoyagi, Kiyoshi; Kawakami, Atsushi

2017-03-01

We evaluated whether the early responsiveness of ultrasound synovitis can predict the clinical response in rheumatoid arthritis (RA) patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs). Articular synovitis was assessed by ultrasound at 22 bilateral wrist and finger joints in 39 RA patients treated with bDMARDs. Each joint was assigned a gray-scale (GS) and power Doppler (PD) score from 0 to 3, and the sum of the GS or PD scores was considered to represent the ultrasound disease activity. We investigated the correlation of the change in ultrasound disease activity at three months with the EULAR response criteria at six months. GS and PD scores were significantly decreased at three months (p < 0.0001). The % changes of the GS and PD scores at three months were significantly higher at six months in moderate and good responders compared with non-responders (p < 0.05). These tendencies were numerically more prominent if clinical response was set as good responder or Disease Activity Score 28 remission. Poor improvement of ultrasound synovitis scores had good predictive value for non-responders at six months. The responsiveness of ultrasound disease activity is considered to predict further clinical response in RA patients treated with bDMARDs.

Association of sleep quality in Behcet disease with disease activity, depression, and quality of life in Korean population

PubMed Central

Lee, Jimin; Kim, Sung-Soo; Jeong, Hye-Jin; Son, Chang-Nam; Kim, Ji-Min; Cho, Yong-Won; Kim, Sang-Hyon

2017-01-01

Background/Aims Sleep disturbance is prime concern in patients with Behcet disease. The purpose of this study was to find out the effects of sleep quality, in Korean patients suffering from Behcet disease. We further investigated the relationship between depression, quality of life and the clinical findings of Behcet disease. Methods The study was performed by the cross-sectional design. Sleep quality was assessed by the Korean version of Pittsburgh sleep quality index (PSQI). Disease activity of Behcet disease was evaluated by Behcet disease current activity form (BDCAF). Depression was assessed by the Korean version of Beck depression inventory second edition (BDI-2). Quality of life was assessed by the Korean version of the Leeds Behcet disease quality of life measure (BDQoL). Results Among the 100 patients studied, 42% reported poor sleep quality (PSQI ≥ 9). These patients have a higher BDI-2, total BDCAF and pain visual analogue scale (VAS) score (p < 0.001, p = 0.022, and p = 0.005). Considering BDCAF, the frequency of genital ulcer was significantly higher (p = 0.01). Behcet was higher in females. The BDQoL was lower in poor sleeper group (p = 0.004 and p < 0.001). Among 7 PSQI components, daytime dysfunction was higher in patients with high disease activity (p = 0.03). Total PSQI score were strongly correlated with BDCAF, BDI-2, BDQoL, and pain VAS score (p = 0.02, p < 0.001, p < 0.001, and p < 0.001, respectively). Conclusions Low sleep quality is directly associated with disease activity, depression, and quality of life in Korean patients with Behcet disease. PMID:28192886

Improving agreement in assessment of synovitis in rheumatoid arthritis.

PubMed

Cheung, Peter P; Dougados, Maxime; Andre, Vincent; Balandraud, Nathalie; Chales, Gérard; Chary-Valckenaere, Isabelle; Chatelus, Emmanuel; Dernis, Emmanuelle; Gill, Ghislaine; Gilson, Mélanie; Guis, Sandrine; Mouterde, Gael; Pavy, Stephan; Pouyol, François; Marhadour, Thierry; Richette, Pascal; Ruyssen-Witrand, Adeline; Soubrier, Martin; Gossec, Laure

2013-03-01

Synovitis assessment through evaluation of swollen joints is integral in steering treatment decisions in rheumatoid arthritis (RA). However, there is high inter-observer variation. The objective was to assess if a short collegiate consensus would improve swollen joint agreement between rheumatologists and whether this was affected by experience. Eighteen rheumatologists from French university rheumatology units participated in three 30 minutes rounds over a half day meeting evaluating joint counts of RA patients in small groups, followed by short consensus discussions. Agreement was evaluated at the end of each round as follows: (i) global agreement of swollen joints (ii) swollen joint agreement according to level of experience of the rheumatologist (iii) swollen joint count and (iv) agreement of disease activity state according to the Disease Activity Score (DAS28). Agreement was calculated using percentage agreement and kappa. Global agreement of swollen joints failed to improve (kappa 0.50 to 0.52) at the joint level. Agreement between seniors did not improve but agreement between newly qualified rheumatologists and their senior peer, which was initially poor (kappa 0.28), improved significantly (to 0.54) at the end of the consensus exercises. Concordance of DAS28 activity states improved from 71% to 87%. Consensus exercises for swollen joint assessment is worthwhile and may potentially improve agreement between clinicians in clinical synovitis and disease activity state, benefit was mostly observed in newly qualified rheumatologists. Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Evaluation of oxidative stress markers and cardiovascular risk factors in Fabry Disease patients

PubMed Central

Müller, Karen B.; Galdieri, Luciano C.; Pereira, Vanessa G.; Martins, Ana M.; D’Almeida, Vânia

2012-01-01

Fabry Disease, an X-linked inborn error of metabolism, is characterized by progressive renal insufficiency, with cardio and cerebrovascular involvement. Homocysteine (Hcy) is considered a risk factor for vascular diseases, but the mechanisms by which it produces cardiovascular damage are still poorly understood. Regarding the vascular involvement in FD patients, the analysis of factors related to thromboembolic events could be useful to improving our understanding of the disease. The aim of this study was to evaluate plasma Hcy and other parameters involved in the methionine cycle, as well as oxidative stress markers. The sample consisted of a group of 10 male FD patients and a control group of 8 healthy individuals, paired by age. Venous blood was collected for Hcy determination, molecular analysis, identification of thiobarbituric acid reactive substances, total glutathione and antioxidant enzymes activity, as well as vitamins quantification. Comparative analysis of FD patients versus the control group indicated hyperhomocysteinemia in 8 of the 10 FD patients, as well as a significant increase in overall glutathione levels and catalase activity. It is inferred that FD patients, apart from activation of the antioxidant system, present increased levels of plasma Hcy, although this is probably unrelated to common alterations in the methionine cycle. PMID:22888289

The potential of volatile organic compounds for the detection of active disease in patients with ulcerative colitis.

PubMed

Smolinska, A; Bodelier, A G L; Dallinga, J W; Masclee, A A M; Jonkers, D M; van Schooten, F-J; Pierik, M J

2017-05-01

To optimise treatment of ulcerative colitis (UC), patients need repeated assessment of mucosal inflammation. Current non-invasive biomarkers and clinical activity indices do not accurately reflect disease activity in all patients and cannot discriminate UC from non-UC colitis. Volatile organic compounds (VOCs) in exhaled air could be predictive of active disease or remission in Crohn's disease. To investigate whether VOCs are able to differentiate between active UC, UC in remission and non-UC colitis. UC patients participated in a 1-year study. Clinical activity index, blood, faecal and breath samples were collected at each out-patient visit. Patients with clear defined active faecal calprotectin >250 μg/g and inactive disease (Simple Clinical Colitis Activity Index <3, C-reactive protein <5 mg/L and faecal calprotectin <100 μg/g) were included for cross-sectional analysis. Non-UC colitis was confirmed by stool culture or radiological evaluation. Breath samples were analysed by gas chromatography time-of-flight mass spectrometry and kernel-based method to identify discriminating VOCs. In total, 72 UC (132 breath samples; 62 active; 70 remission) and 22 non-UC-colitis patients (22 samples) were included. Eleven VOCs predicted active vs. inactive UC in an independent internal validation set with 92% sensitivity and 77% specificity (AUC 0.94). Non-UC colitis patients could be clearly separated from active and inactive UC patients with principal component analysis. Volatile organic compounds can accurately distinguish active disease from remission in UC and profiles in UC are clearly different from profiles in non-UC colitis patients. VOCs have demonstrated potential as new non-invasive biomarker to monitor inflammation in UC. © 2017 John Wiley & Sons Ltd.

A Pilot Evaluation of an Art Therapy Program for Refugee Youth from Burma

ERIC Educational Resources Information Center

Kowitt, Sarah Dorothy; Emmerling, Dane; Gavarkavich, Diane; Mershon, Claire-Helene; Linton, Kristin; Rubesin, Hillary; Agnew-Brune, Christine; Eng, Eugenia

2016-01-01

Art therapy is a promising form of therapy to address mental health concerns for refugee youth. This article describes the development and implementation of a pilot evaluation of an art therapy program for refugee adolescents from Burma currently living in the United States. Evaluation activities were based on the Centers for Disease Control and…

A randomized controlled cross-over trial investigating the effect of anti-inflammatory diet on disease activity and quality of life in rheumatoid arthritis: the Anti-inflammatory Diet In Rheumatoid Arthritis (ADIRA) study protocol.

PubMed

Winkvist, Anna; Bärebring, Linnea; Gjertsson, Inger; Ellegård, Lars; Lindqvist, Helen M

2018-04-20

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects 0.5-1.0% of the population, and where many patients in spite of modern pharmacological treatment fail to reach remission. This affects physical as well as mental wellbeing and leads to severely reduced quality of life and reduced work capacity, thus yielding high individual as well as societal costs. As a complement to modern pharmacological treatment, lifestyle intervention should be evaluated as a treatment option. Scientific evidence exists for anti-inflammatory effects by single foods on RA, but no study exists where these foods have been combined to obtain maximum effect and thus offer a substantial improvement in patient life quality. The main goal of the randomized cross-over trial ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis) is to test the hypothesis that an anti-inflammatory diet intervention, compared to a regular diet, will decrease disease activity and improve quality of life in patients with stable established RA. In total, 50 RA patients with moderate disease activity are randomized to receive initially either a portfolio diet based on several food items with suggested anti-inflammatory effects or a control diet during 2 × 10 weeks with 3 months wash-out between diets. Food bags are delivered weekly by a home food delivery chain and referred to as the fiber bag and the protein bag, respectively, to partially blind participants. Both groups continue with regular pharmacological treatment. Known food biomarkers will be analyzed to measure intervention compliance. Impact on disease severity (measured by DAS28, a composite score which predicts disability and progression of RA), risk markers for cardiovascular disease and quality of life are evaluated after each diet regimen. Metabolomics will be used to evaluate the potential to predict responders to dietary treatment. A health economic evaluation is also included. The nutritional status of patients with RA often is poor and many ask their physician for diet advice. No evidence-based dietary guidelines for patients with RA exist because of the paucity of well-conducted sufficiently large diet intervention trials. ADIRA is an efficacy study and will provide evidence as to whether dietary treatment of RA can reduce disease activity and improve quality of life as well as reduce individual and societal costs. ClinicalTrials.gov Registration Number: NCT02941055 .

Psychological distress, iron deficiency, active disease and female gender are independent risk factors for fatigue in patients with ulcerative colitis

PubMed Central

Jonefjäll, Börje; Simrén, Magnus; Lasson, Anders; Öhman, Lena; Strid, Hans

2017-01-01

Background Patients with ulcerative colitis often report fatigue. Objectives To investigate prevalence of and risk factors for fatigue in patients with ulcerative colitis with active disease and during deep remission. Methods In this cross-sectional study, disease activity was evaluated with endoscopy and calprotectin, and patients were classified as having active disease (n = 133) or being in deep remission (n = 155). Blood samples were analysed to assess anaemia, iron deficiency and systemic immune activity. Patients completed questionnaires to assess fatigue, psychological distress, gastrointestinal symptoms and quality of life. Results The prevalence of high fatigue (general fatigue ≥ 13, Multidimensional Fatigue Inventory) was 40% in the full study population. Among patients with high fatigue, female gender and iron deficiency were more prevalent, and these patients had more severe disease activity and reported higher levels of anxiety, depression and decreased quality of life compared with patients with no/mild fatigue. A logistic regression analysis identified probable psychiatric disorder (odds ratio (OR) (confidence interval) 6.1 (3.1–12.2)), iron deficiency (OR 2.5 (1.2–5.1)), active disease (OR 2.2 (1.2–3.9)) and female gender (OR 2.1 (1.1–3.7)) as independent risk factors for high fatigue. Similar results were found concerning psychological distress, gender and quality of life, but immune markers did not differ in patients in deep remission with high vs. no/mild fatigue. Conclusions Probable psychiatric disorder, iron deficiency, active disease and female gender are independent risk factors for high fatigue in patients with ulcerative colitis. Low-grade immune activity does not seem to be the cause of fatigue among patients in deep remission. PMID:29435325

Reduced cortical activation in inferior frontal junction in Unverricht-Lundborg disease (EPM1) - A motor fMRI study.

PubMed

Könönen, Mervi; Danner, Nils; Koskenkorva, Päivi; Kälviäinen, Reetta; Hyppönen, Jelena; Mervaala, Esa; Karjalainen, Pasi; Vanninen, Ritva; Niskanen, Eini

2015-03-01

Unverricht-Lundborg disease (EPM1) is characterized by stimulus-sensitive and action-activated myoclonus, tonic-clonic seizures and ataxia. Several disease-related alterations in cortical structure and excitability have been associated with the motor symptoms of EPM1. This study aimed to elucidate possible alterations in cortical activation related to motor performance in EPM1. Fifteen EPM1-patients and 15 healthy volunteers matched for age and sex underwent motor functional MRI. Group differences in activations were evaluated in the primary and supplementary motor cortices and sensory cortical areas. Furthermore, in EPM1 patients, the quantitative fMRI parameters were correlated with the severity of the motor symptoms. The EPM1-patients exhibited decreased activation in the left inferior frontal junction (IFJ) during right hand voluntary motor task when compared with controls. In the quantitative analysis, EPM1-patients had significantly weaker activation than controls in the hand knob and supplementary motor areas (SMA). The volume of activation in M1 decreased with age and duration of disease in the patient group, whereas the volume increased with age in controls. Negative correlations were observed between fMRI parameters of SMA and disease duration or age in patients but not in controls. The weaker motor fMRI activation observed in EPM1 patients parallels previous neurophysiological findings and correlates with the motor symptoms of the disease. Thus, the observed decrease in IFJ activation in EPM1 patients may be associated with the difficulties in initiation or termination of motor execution, a typical clinical symptom in EPM1. The fMRI findings reflect the progressive nature of this disease. Copyright © 2015 Elsevier B.V. All rights reserved.

[Development of an instrument to measure psychosocial determinants of physical activity behavior among coronary heart disease patients].

PubMed

Mendez, Roberto Della Rosa; Rodrigues, Roberta Cunha Matheus; Cornélio, Marilia Estevam; Gallani, Maria Cecília Bueno Jayme; Godin, Gaston

2010-09-01

The aim of this study was to report the development and the analysis of content validity and reliability of the Psychosocial Determinants of Physical Activity among Coronary Heart Disease Patients Questionnaire, based on an extension of the Theory of Planned Behavior. In the content validity step, three experts evaluated the instrument which was, afterwards, pre-tested with five subjects in order to obtain a conceptually appropriate and easily understood instrument. Fifty-one patients participated in the evaluation of internal consistency of the reviewed instrument. Cronbach's alpha coefficients above 0.75 were observed for the constructs: Intention, Attitude, Subjective Norm, Self-efficacy and Habit. The new instrument demonstrated acceptable evidence of content validity and reliability.

Laboratory diagnosis of von Willebrand's disease.

PubMed

Rick, M E

1994-12-01

The diagnosis of von Willebrand's disease is becoming complex as more is understood about the disease. Clinical information and laboratory data are necessary for the diagnosis because of the overlap of normal and abnormal laboratory values. A complete evaluation including von Willebrand factor multimers, ristocetin-induced platelet aggregation, factor VIII activity level, and a template bleeding time is necessary to correctly classify the patient so that optimal treatment may be given.

Circulating Follicular Helper-Like T Cells in Systemic Lupus Erythematosus: Association with Disease Activity

PubMed Central

Choi, Jin-Young; Ho, John Hsi-en; Pasoto, Sandra G; Bunin, Viviane; Kim, Sangtaek; Carrasco, Solange; Borba, Eduardo F; Gonçalves, Celio R; Costa, Priscila R; Kallas, Esper G; Bonfa, Eloisa; Craft, Joe

2015-01-01

Objective To assess circulating follicular helper-like CD4+ T (cTfh-like) cells in systemic lupus erythematosus (SLE) and determine their relationship to disease activity. Methods We analyzed blood samples from SLE patients, and as controls, Behçet’s disease (BD) patients and healthy individuals. We used flow cytometry to enumerate cTfh-like cells using as markers the C-X-C chemokine receptor type 5 (CXCR5), inducible T-cell costimulator (ICOS), programmed cell death protein-1 (PCDC1, PD-1), and secretion of interleukin-21 (IL-21). We compared the frequency of cTfh-like cells with that of circulating plasmablasts (CD19+IgD−CD38+) and evaluated their possible association with disease activity. Results cTfh-like T cells, identified as CXCR5hiICOShiPD-1hi, were expanded in the blood of SLE patients compared to BD and healthy controls. Such cells produced IL-21 with lower expression of CCR7, compared to circulating CXCR5hi central memory (Tcm) cells, enabling their distinction. PD-1, not ICOS or CXCR5, expression was significantly elevated in cTfh-like cells from SLE patients compared to controls. PD-1 expression among CXCR5hi cTfh-like cells correlated with disease activity, circulating plasmablasts, and anti-dsDNA antibody positivity, but not disease duration nor past organ injury; rather, it reflected current active disease. Conclusion We found that cTfh-like cells are associated with disease activity in SLE, suggesting that their presence indicates abnormal homeostasis of T-B cell collaboration with a causal relationship central to disease pathogenesis. These findings also suggest that cTfh-like cells provide a surrogate for aberrant GC activity in SLE, and that their PD-1 expression offers a tool for following disease activity and response to therapies. PMID:25581113

Pasos Adelante: the effectiveness of a community-based chronic disease prevention program.

PubMed

Staten, Lisa K; Scheu, Linda L; Bronson, Dan; Peña, Veronica; Elenes, JoJean

2005-01-01

Implementing programs that target primary prevention of chronic diseases is critical for at-risk populations. Pasos Adelante, or "Steps Forward," is a curriculum aimed at preventing diabetes, cardiovascular disease, and other chronic diseases in Hispanic populations. Pasos Adelante is adapted from the National Heart, Lung, and Blood Institute's cardiovascular disease prevention curriculum, Su Corazon, Su Vida, and includes sessions on diabetes and community advocacy and incorporates walking clubs. The Pasos Adelante curriculum was implemented in two Arizona, United States-Sonora, Mexico border counties. Key issues in these communities are safety, access to recreational facilities, climate, and cultural beliefs. Pasos Adelante is a 12-week program facilitated by community health workers. The program includes interactive sessions on chronic disease prevention, nutrition, and physical activity. Evaluation of the program included precurriculum and postcurriculum questionnaires with self-reported measures of physical activity and dietary patterns. Approximately 250 people participated in the program in Yuma and Santa Cruz counties. Postprogram evaluation results demonstrate a significant increase in moderate to vigorous walking among participants and shifts in nutritional patterns. The Pasos Adelante program demonstrates that an educational curriculum in conjunction with the support of community health workers can motivate people in Arizona/Sonora border communities to adopt healthy lifestyle behaviors.

Ultrasound-detected bone erosion is a relapse risk factor after discontinuation of biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis whose ultrasound power Doppler synovitis activity and clinical disease activity are well controlled.

PubMed

Kawashiri, Shin-Ya; Fujikawa, Keita; Nishino, Ayako; Okada, Akitomo; Aramaki, Toshiyuki; Shimizu, Toshimasa; Umeda, Masataka; Fukui, Shoichi; Suzuki, Takahisa; Koga, Tomohiro; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Mizokami, Akinari; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Aoyagi, Kiyoshi; Maeda, Takahiro; Kawakami, Atsushi

2017-05-25

In the present study, we explored the risk factors for relapse after discontinuation of biologic disease-modifying antirheumatic drug (bDMARD) therapy in patients with rheumatoid arthritis (RA) whose ultrasound power Doppler (PD) synovitis activity and clinical disease activity were well controlled. In this observational study in clinical practice, the inclusion criteria were based on ultrasound disease activity and clinical disease activity, set as low or remission (Disease Activity Score in 28 joints based on erythrocyte sedimentation rate <3.2). Ultrasound was performed in 22 joints of bilateral hands at discontinuation for evaluating synovitis severity and presence of bone erosion. Patients with a maximum PD score ≤1 in each joint were enrolled. Forty patients with RA were consecutively recruited (November 2010-March 2015) and discontinued bDMARD therapy. Variables at the initiation and discontinuation of bDMARD therapy that were predictive of relapse during the 12 months after discontinuation were assessed. The median patient age was 54.5 years, and the median disease duration was 3.5 years. Nineteen (47.5%) patients relapsed during the 12 months after the discontinuation of bDMARD therapy. Logistic regression analysis revealed that only the presence of bone erosion detected by ultrasound at discontinuation was predictive of relapse (OR 8.35, 95% CI 1.78-53.2, p = 0.006). No clinical characteristics or serologic biomarkers were significantly different between the relapse and nonrelapse patients. The ultrasound synovitis scores did not differ significantly between the groups. Our findings are the first evidence that ultrasound bone erosion may be a relapse risk factor after the discontinuation of bDMARD therapy in patients with RA whose PD synovitis activity and clinical disease activity are well controlled.

38 CFR 3.310 - Disabilities that are proximately due to, or aggravated by, service-connected disease or injury.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Dependency and Indemnity Compensation Ratings and Evaluations; Service Connection § 3.310 Disabilities that... or injury shall be service connected. When service connection is thus established for a secondary... current level of severity of the nonservice-connected disease or injury. The rating activity will...

Subthalamic Nucleus Stimulation and Dysarthria in Parkinson's Disease: A PET Study

ERIC Educational Resources Information Center

Pinto, Serge; Thobois, Stephane; Costes, Nicolas; Le Bars, Didier; Benabid, Alim-Louis; Broussolle, Emmanuel; Pollak, Pierre; Gentil, Michele

2004-01-01

In Parkinson's disease, functional imaging studies during limb motor tasks reveal cerebral activation abnormalities that can be reversed by subthalamic nucleus (STN) stimulation. The effect of STN stimulation on parkinsonian dysarthria has not, however, been investigated using PET. The aim of the present study was to evaluate the effect of STN…

76 FR 20993 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-14

... delivered by the SCDNBSP and SCDTDP networks to individuals affected by sickle cell disease who present at... review by the Office of Management and Budget (OMB), in compliance with the Paperwork Reduction Act of... Act of 1995: Proposed Project: Sickle Cell Disease Program Evaluations and Quality Improvement...

The Preventive Control of Zoonotic Visceral Leishmaniasis: Efficacy and Economic Evaluation

PubMed Central

Wu, Jianhong; Massad, Eduardo

2017-01-01

Zoonotic Visceral Leishmaniasis (ZVL) is one of the world's deadliest and neglected infectious diseases, according to World Health Organization. This disease is one of major human and veterinary medical significance. The sandfly and the reservoir in urban areas remain among the major challenges for the control activities. In this paper, we evaluated five control strategies (positive dog elimination, insecticide impregnated dog collar, dog vaccination, dog treatment, and sandfly population control), considering disease control results and cost-effectiveness. We elaborated a mathematical model based on a set of differential equations in which three populations were represented (human, dog, and sandfly). Humans and dogs were divided into susceptible, latent, clinically ill, and recovery categories. Sandflies were divided into noninfected, infected, and infective. As the main conclusions, the insecticide impregnated dog collar was the strategy that presented the best combination between disease control and cost-effectiveness. But, depending on the population target, the control results and cost-effectiveness of each strategy may differ. More and detailed studies are needed, specially one which optimizes the control considering more than one strategy in activity. PMID:28588642

The Preventive Control of Zoonotic Visceral Leishmaniasis: Efficacy and Economic Evaluation.

PubMed

Shimozako, Helio Junji; Wu, Jianhong; Massad, Eduardo

2017-01-01

Zoonotic Visceral Leishmaniasis (ZVL) is one of the world's deadliest and neglected infectious diseases, according to World Health Organization. This disease is one of major human and veterinary medical significance. The sandfly and the reservoir in urban areas remain among the major challenges for the control activities. In this paper, we evaluated five control strategies (positive dog elimination, insecticide impregnated dog collar, dog vaccination, dog treatment, and sandfly population control), considering disease control results and cost-effectiveness. We elaborated a mathematical model based on a set of differential equations in which three populations were represented (human, dog, and sandfly). Humans and dogs were divided into susceptible, latent, clinically ill, and recovery categories. Sandflies were divided into noninfected, infected, and infective. As the main conclusions, the insecticide impregnated dog collar was the strategy that presented the best combination between disease control and cost-effectiveness. But, depending on the population target, the control results and cost-effectiveness of each strategy may differ. More and detailed studies are needed, specially one which optimizes the control considering more than one strategy in activity.

Activity of lycorine analogs against the fish bacterial pathogen Flavobacterium columnare

USDA-ARS?s Scientific Manuscript database

In a continuing effort to discover natural products and natural product-based compounds for the control of columnaris disease in channel catfish (Ictalurus punctatus), seventeen lycorine analogs were synthesized, including new benzoyl analogs 6 – 16, and evaluated for antibacterial activity against ...

Minimizing off-Target Mutagenesis Risks Caused by Programmable Nucleases

PubMed Central

Ishida, Kentaro; Gee, Peter; Hotta, Akitsu

2015-01-01

Programmable nucleases, such as zinc finger nucleases (ZFNs), transcription activator like effector nucleases (TALENs), and clustered regularly interspersed short palindromic repeats associated protein-9 (CRISPR-Cas9), hold tremendous potential for applications in the clinical setting to treat genetic diseases or prevent infectious diseases. However, because the accuracy of DNA recognition by these nucleases is not always perfect, off-target mutagenesis may result in undesirable adverse events in treated patients such as cellular toxicity or tumorigenesis. Therefore, designing nucleases and analyzing their activity must be carefully evaluated to minimize off-target mutagenesis. Furthermore, rigorous genomic testing will be important to ensure the integrity of nuclease modified cells. In this review, we provide an overview of available nuclease designing platforms, nuclease engineering approaches to minimize off-target activity, and methods to evaluate both on- and off-target cleavage of CRISPR-Cas9. PMID:26501275

Talk the talk and walk the walk. Evaluation of autonomy in aging and Alzheimer disease by simulating instrumental activities of daily living: the S-IADL

PubMed Central

Gounden, Yannick; Lacot, Emilie; Couvillers, Frédérique; Lions, Amandine; Hainselin, Mathieu

2016-01-01

Objective The autonomy of individuals is linked to the achievement of instrumental activities of daily living that require complex behavior. In the elderly, the assessment of autonomy is usually based on questionnaires that have strong subjective constraints. Considering this fact, we tested elderly healthy adults and Alzheimer disease patients using a new measure, the S-IADL (Simulation of Instrumental Activities for Daily Living), to assess the ability to perform effectively activities of daily living. Method The S-IADL shares many items with the well-known IADL questionnaire proposed by Lawton & Brody (1969). However, as opposed to the IADL, the assessment of autonomy is not based on the completion of a questionnaire but requires the realization or simulation of various activities of daily living. Eighty-three participants (69 healthy elderly, and 14 Alzheimer Disease patients) completed the IADL and performed the S-IADL assessment. Results Results revealed that, like the IADL, the S-IADL is able to identify AD patients who are likely to encounter difficulties in performing everyday activities, and no major differences were found between the IADL and the S-IADL. Conclusions We outlined some advantages for prefering, in certain situation, this new tool based on simulation of activities in functional evaluation. Finally, we discuss the main limits of the S-IADL that should be investigated prior to its utilization by clinicians. PMID:27672491

PrEFiNe Plan: Strategic plan for Fabry diseases in Nephrology.

PubMed

Del Pino, M D; Ortiz, A; Torra, R; Hernandez, D

2016-01-01

Renal failure is one of the main causes of death in patients with Fabry disease (FD). Due to the low prevalence of FD, delayed diagnosis and misdiagnosis, often the correct diagnosis is made when organ damage is already present. Early recognition of the disease would allow the prevention of severe complications and the premature death of patients with FD. We present here the PrEFiNE project, which includes a wide spectrum of activities with the aim of improve knowledge and diagnosis of FD. The project is sponsored by Shire Iberia (http://shireiberica.com/) From January 2016 to the end of 2017 several activities will be carried out, starting with a survey to evaluate current FD knowledge among nephrologists; in addition some studies to assess prevalence of this disease will be performed. One study will include patients receiving dialysis, another study will cover kidney transplant patients, and a pilot study in chronic kidney disease in stage 3-5 predialysis. Also planned is a pharmacoeconomic study to focus on burden of FD. At the same time medical education activities will be conducted both on line and on site. Plan for dissemination will include medical publications and diffusion to media. PrEFiNE Project will finish with the publication of a compilation book on FD in Nephrology including all planned activities and proposing recommendations based on results and detected unmet needs. PrEfiNE Plan will be coordinated by severa scientific committees, one at national level and 10 other regionals comittees, tha will be responsible to ensure the maximum scientific quality of proposed activities. An advisory board will supervise the project. PrEfiNE project will evaluate an action plan focused on improving FD knowledge to make necessary recommendations for an early recognition of the disease. In addition will generate a plan to improve previously undetected needs. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Accelerator Production and Separations for High Specific Activity Rhenium-186

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

Jurisson, Silvia S.; Wilbur, D. Scott

2016-04-01

Tungsten and osmium targets were evaluated for the production of high specific activity rhenium-186. Rhenium-186 has potential applications in radiotherapy for the treatment of a variety of diseases, including targeting with monoclonal antibodies and peptides. Methods were evaluated using tungsten metal, tungsten dioxide, tungsten disulfide and osmium disulfide. Separation of the rhenium-186 produced and recycling of the enriched tungsten-186 and osmium-189 enriched targets were developed.

Platelet monoamine oxidase B and plasma β-phenylethylamine in Parkinson's disease

PubMed Central

Zhou, G; Miura, Y; Shoji, H; Yamada, S; Matsuishi, T

2001-01-01

OBJECTIVE—To evaluate the correlation between changes in platelet monoamine oxidase type B (MAO-B) activity and plasma β-phenylethylamine (PEA) concentrations in patients with Parkinson's disease and controls.
METHODS—Platelet MAO-B activity and plasma PEA were measured with gas chromatography-mass spectrometry (GC-MS) in patients with Parkinson's disease treated with levodopa (12 men and 12 women) or selegiline (three men and three women), and physically healthy subjects as a control group (10 men and 10women).
RESULTS—Platelet MAO-B activity was significantly higher in the Parkinson's disease group (mean 542 (SD 318) pmol/107 platelets/30 min) than in the control group (mean 349 (SD 307) pmol/107 platelets/30 min) (p<0.05). By contrast, the plasma PEA concentrations in patients with Parkinson's disease were significantly lower than in the control group (mean 532 (SD 243) pg/ml; 931 (SD 560) pg/ml) (p<0.01). The plasma PEA concentrations in patients with Parkinson's disease treated with selegiline were prominently higher than in patients with no selegiline treatment (p<0.001). There was a significantly negative correlation between platelet MAO-B activity and plasma PEA concentrations in patients (n=24, r=−0.466, p<0.001).
CONCLUSIONS—The increase in platelet MAO-B activity and decrease in plasma PEA concentrations in patients with Parkinson's disease may be involved in the pathophysiological processes of the disease, and these changes are reversed by treatment with selegiline.

 PMID:11160474

Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer's disease.

PubMed

Mury, Fábio B; da Silva, Weber C; Barbosa, Nádia R; Mendes, Camila T; Bonini, Juliana S; Sarkis, Jorge Eduardo Souza; Cammarota, Martin; Izquierdo, Ivan; Gattaz, Wagner F; Dias-Neto, Emmanuel

2016-10-01

Phospholipase A2 (Pla2) is required for memory retrieval, and its inhibition in the hippocampus has been reported to impair memory acquisition in rats. Moreover, cognitive decline and memory deficits showed to be reduced in animal models after lithium treatment, prompting us to evaluate possible links between Pla2, lithium and memory. Here, we evaluated the possible modulation of Pla2 activity by a long-term treatment of rats with low doses of lithium and its impact in memory. Wistar rats were trained for the inhibitory avoidance task, treated with lithium for 100 days and tested for perdurability of long-term memory. Hippocampal samples were used for quantifying the expression of 19 brain-expressed Pla2 genes and for evaluating the enzymatic activity of Pla2 using group-specific radio-enzymatic assays. Our data pointed to a significant perdurability of long-term memory, which correlated with increased transcriptional and enzymatic activities of certain members of the Pla2 family (iPla2 and sPla2) after the chronic lithium treatment. Our data suggest new possible targets of lithium, add more information on its pharmacological activity and reinforce the possible use of low doses of lithium for the treatment of neurodegenerative conditions such as the Alzheimer's disease.

Biological Evaluation and Molecular Docking of Protocatechuic Acid from Hibiscus sabdariffa L. as a Potent Urease Inhibitor by an ESI-MS Based Method.

PubMed

Hassan, Sherif T S; Švajdlenka, Emil

2017-10-11

Studies on enzyme inhibition remain a crucial area in drug discovery since these studies have led to the discoveries of new lead compounds useful in the treatment of several diseases. In this study, protocatechuic acid (PCA), an active compound from Hibiscus sabdariffa L. has been evaluated for its inhibitory properties against jack bean urease (JBU) as well as its possible toxic effect on human gastric epithelial cells (GES-1). Anti-urease activity was evaluated by an Electrospray Ionization-Mass Spectrometry (ESI-MS) based method, while cytotoxicity was assayed by the MTT method. PCA exerted notable anti-JBU activity compared with that of acetohydroxamic acid (AHA), with IC 50 values of 1.7 and 3.2 µM, respectively. PCA did not show any significant cytotoxic effect on (GES-1) cells at concentrations ranging from 1.12 to 3.12 µM. Molecular docking study revealed high spontaneous binding ability of PCA to the active site of urease. Additionally, the anti-urease activity was found to be related to the presence of hydroxyl moieties of PCA. This study presents PCA as a natural urease inhibitor, which could be used safely in the treatment of diseases caused by urease-producing bacteria.

Long-Term Effects of (–)-Epigallocatechin Gallate (EGCG) on Pristane-Induced Arthritis (PIA) in Female Dark Agouti Rats

PubMed Central

Leichsenring, Anna; Bäcker, Ingo; Furtmüller, Paul G.; Obinger, Christian; Lange, Franziska; Flemmig, Jörg

2016-01-01

Rheumatoid arthritis (RA)—a widespread chronic inflammatory disease in industrialized countries—is characterized by a persistent and progressive joint destruction. The chronic pro-inflammatory state results from a mutual activation of the innate and the adaptive immune system, while the exact pathogenesis mechanism is still under discussion. New data suggest a role of the innate immune system and especially polymorphonuclear granulocytes (PMNs, neutrophils) not only during onset and the destructive phase of RA but also at the chronification of the disease. Thereby the enzymatic activity of myeloperoxidase (MPO), a peroxidase strongly abundant in neutrophils, may be important: While its peroxidase activity is known to contribute to cartilage destruction at later stages of RA the almost MPO-specific oxidant hypochlorous acid (HOCl) is also discussed for certain anti-inflammatory effects. In this study we used pristane-induced arthritis (PIA) in Dark Agouti rats as a model for the chronic course of RA in man. We were able to shown that a specific detection of the HOCl-producing MPO activity provides a sensitive new marker to evaluate the actual systemic inflammatory status which is only partially detectable by the evaluation of clinical symptoms (joint swelling and redness measurements). Moreover, we evaluated the long-term pharmacological effect of the well-known anti-inflammatory flavonoid epigallocatechin gallate (EGCG). Thereby only upon early and continuous oral application of this polyphenol the arthritic symptoms were considerably diminished both in the acute and in the chronic phase of the disease. The obtained results were comparable to the treatment control (application of methotrexate, MTX). As revealed by stopped-flow kinetic measurements, EGCG may regenerate the HOCl-production of MPO which is known to be impaired at chronic inflammatory diseases like RA. It can be speculated that this MPO activity-promoting effect of EGCG may contribute to the pharmacological mode of action of this polyphenol. PMID:27023113

Regional differences in baseline disease activity and remission rates following golimumab treatment for RA: results from the GO-MORE trial.

PubMed

Durez, Patrick; Pavelka, Karel; Lazaro, Maria Alicia; Garcia-Kutzbach, Abraham; Moots, Robert J; Amital, Howard; Govoni, Marinella; Vastesaeger, Nathan

2018-05-01

GO-MORE (NCT00975130) was a large open-label, multinational, multicenter, prospective phase 3 trial evaluating add-on therapy with golimumab in biologic-naïve patients with active rheumatoid arthritis (RA). The objective of this post hoc analysis was to examine regional differences in baseline disease activity and remission rates following golimumab treatment for RA. This was a planned, descriptive post hoc analysis of data from the GO-MORE trial. Baseline disease activity and remission were defined as moderate or severe based on EULAR criteria. This analysis included 3280 participants from the GO-MORE trial. All participants included in this analysis had high or moderate disease activity at baseline. At baseline, high disease activity was least common in Europe (71.0%), Canada (77.0%), and the Middle East (78.2%) and most common in Latin America (90.7%), South Africa (91.5%), and Asia (92.5%). Month 6 remission rates were highest in South Africa (29.1%), Europe (27.9%), and the Middle East (27.3%) and lowest in Canada (19.7%), Latin America (17.2%), and Asia (15.0%). Higher rates of remission in each geographical region generally corresponded with lower baseline disease activity. We suspect that access to care and implementation of the treat-to-target strategy were the most important determinants, but this apparent relationship needs to be confirmed in further studies that include a statistical analysis of prognostic indicators.

Thalidomide analogues: Tumor necrosis factor-alpha inhibitors and their evaluation as anti-inflammatory agents.

PubMed

Casal, Juan José; Bollini, Mariela; Lombardo, María Elisa; Bruno, Ana María

2016-02-15

A series of related thalidomide derivatives (2-9) were synthesized by microwave irradiation and evaluated for anti-inflammatory activity. Such activity was assessed in vivo and ex vivo. Compounds 2, 8 and 9 showed the highest levels of inhibition of TNF-α production. On rat paw edema and hyperalgesia assays, compound 9, (1,4-phthalazinedione) demonstrated the highest in vivo anti-inflammatory activity. Thus, compound 9 can be considered as a promising compound to be subjected to further modification to obtain new agents for the treatment of inflammatory diseases.

Advances in the Evaluation of Respiratory Pathophysiology during Exercise in Chronic Lung Diseases

PubMed Central

O'Donnell, Denis E.; Elbehairy, Amany F.; Berton, Danilo C.; Domnik, Nicolle J.; Neder, J. Alberto

2017-01-01

Dyspnea and exercise limitation are among the most common symptoms experienced by patients with various chronic lung diseases and are linked to poor quality of life. Our understanding of the source and nature of perceived respiratory discomfort and exercise intolerance in chronic lung diseases has increased substantially in recent years. These new mechanistic insights are the primary focus of the current review. Cardiopulmonary exercise testing (CPET) provides a unique opportunity to objectively evaluate the ability of the respiratory system to respond to imposed incremental physiological stress. In addition to measuring aerobic capacity and quantifying an individual's cardiac and ventilatory reserves, we have expanded the role of CPET to include evaluation of symptom intensity, together with a simple “non-invasive” assessment of relevant ventilatory control parameters and dynamic respiratory mechanics during standardized incremental tests to tolerance. This review explores the application of the new advances in the clinical evaluation of the pathophysiology of exercise intolerance in chronic obstructive pulmonary disease (COPD), chronic asthma, interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). We hope to demonstrate how this novel approach to CPET interpretation, which includes a quantification of activity-related dyspnea and evaluation of its underlying mechanisms, enhances our ability to meaningfully intervene to improve quality of life in these pathologically-distinct conditions. PMID:28275353

Metabolic and cardiovascular outcomes in patients with Cushing's syndrome of different aetiologies during active disease and 1 year after remission.

PubMed

Giordano, Roberta; Picu, Andreea; Marinazzo, Elisa; D'Angelo, Valentina; Berardelli, Rita; Karamouzis, Ioannis; Forno, Daniela; Zinnà, Domenico; Maccario, Mauro; Ghigo, Ezio; Arvat, Emanuela

2011-09-01

Cushing's syndrome is associated with several comorbidities responsible for the increased cardiovascular risk, not only during the active phase but also after disease remission. In 29 patients with Cushing's syndrome (14 Cushing's diseases and 15 adrenal adenomas), waist circumference, fasting and 2-h glucose after oral glucose tolerance test (OGTT), lipid profile and blood pressure were evaluated during the active disease and 1 year after remission and compared with those in 29 sex-, age- and BMI-matched controls. During the active disease, waist circumference, 2-h glucose after OGTT, total and LDL cholesterol were higher in patients with Cushing's syndrome than in controls (P < 0·001) but similar in Cushing's disease and adrenal adenomas. The prevalence of impaired glucose tolerance (IGT), diabetes mellitus, dyslipidaemia and hypertension was higher (P < 0·001) in patients with Cushing's syndrome (27%, 24%, 59% and 72%) than in controls (10%, 0%, 21% and 10%), with no significant difference between Cushing's disease and adrenal adenomas. One year following hormonal remission, waist circumference persisted higher than in controls (P < 0·05) in both Cushing's disease and adrenal adenomas. Metabolic and cardiovascular abnormalities were still present in both groups, although with a lower prevalence, as well as with a more marked decrease in adrenal adenomas (P < 0·05 vs active disease for IGT, dyslipidaemia and hypertension). These results show that chronic hypercortisolism, independently of its aetiology, contributes to metabolic impairment and increased cardiovascular risk, while these abnormalities mostly persist in patients with previous Cushing's disease after hormonal remission. Pituitary hormonal deficiencies, hormonal replacement treatments and/or incomplete cure from Cushing's disease may account for these findings. © 2011 Blackwell Publishing Ltd.

Influence of Education on Disease Activity and Damage in Systemic Lupus Erythematosus: Data From the 1000 Canadian Faces of Lupus.

PubMed

George, Angela; Wong-Pak, Andrew; Peschken, Christine A; Silverman, Earl; Pineau, Christian; Smith, C Douglas; Arbillaga, Hector; Zummer, Michel; Bernatsky, Sasha; Hudson, Marie; Hitchon, Carol; Fortin, Paul R; Nevskaya, Tatiana; Pope, Janet E

2017-01-01

To determine whether socioeconomic status assessed by education is associated with disease activity and the risk of organ damage in systemic lupus erythematosus (SLE). Data from the 1000 Canadian Faces of Lupus, a multicenter database of adult SLE patients, was used to compare education as either low (did not complete high school) or high (completed high school or further) for disease activity and damage. Education was also studied as a continuous variable. The relationships between education and SLE outcomes (any organ damage defined as a Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI] score ≥1, serious organ damage [SDI score ≥3], and end-stage renal disease) were evaluated using logistic regression analyses adjusted for age, sex, race/ethnicity, and disease duration. A total of 562 SLE patients met inclusion criteria (mean age 47 years, 91% female, and mean disease duration of 10 years); 81% had high education. The low education group was twice as likely to be work disabled (30%; P < 0.0001); they had higher disease activity and reduced renal function. Linear regression analysis revealed that low education was significantly associated with higher disease activity at enrollment into the 1000 Canadian Faces of Lupus database, after adjustment for age (at entry and at diagnosis), race/ethnicity, and sex (B 1.255 + 0.507 [SE], β = 0.115, P = 0.014). In our adjusted logistic regression models we were unable to demonstrate significant associations between education and SLE damage. Results did not change when varying the education variable. In this cohort, low education was associated cross-sectionally with higher disease activity and work disability, but not damage. © 2016, American College of Rheumatology.

Is physical exercise a multiple sclerosis disease modifying treatment?

PubMed

Motl, Robert W; Pilutti, Lara A

2016-08-01

There is consensus that exercise represents a behavioral approach for the restoration of function and management of symptoms among persons with multiple sclerosis (MS). The current paper provides a review on the topic of exercise and physical activity as MS-disease modifying treatments. Firstly, metrics for evaluating disease modification and progression in MS are described. Secondly, evidence for exercise as a MS-disease modifying therapy based on individual studies, literature reviews, and meta-analyses is summarized. Finally, the paper focuses on major limitations of the existing body of research. Expert commentary: Exercise and physical activity have been associated with reduced relapse rate, mobility disability and its progression, and lesion volume, and improved neuroperformance, particularly walking outcomes. This evidence provides a positive, yet preliminary, picture for exercise having possible effects on markers of disease modification and progression in MS.

Learned helplessness in the multiple sclerosis population.

PubMed

McGuinness, S

1996-06-01

The purpose of this cross-sectional, descriptive study was to describe the relationships between learned helplessness and disease status, functional and social disability, and disease activity in the multiple sclerosis population. Additionally, the relationships between learned helplessness and age, disease duration, education and marital and employment status were evaluated. Self-report instruments with established validity and reliability in the multiple sclerosis population were used to collect the data. Learned helplessness was significantly positively correlated with social and functional disability. Although not significant at the .05 level, disease status and disease activity were also positively correlated with learned helplessness. Additionally, unemployed individuals were more likely to be helpless than employed individuals. Overall, the results suggest that learned helplessness is related to negative health indicators in the multiple sclerosis population. Nursing interventions to decrease or prevent learned helplessness may be appropriate in this population.

Safety and effectiveness of iguratimod in patients with rheumatoid arthritis: Final report of a 52-week, multicenter postmarketing surveillance study.

PubMed

Mimori, Tsuneyo; Harigai, Masayoshi; Atsumi, Tatsuya; Fujii, Takao; Kuwana, Masataka; Matsuno, Hiroaki; Momohara, Shigeki; Takei, Syuji; Tamura, Naoto; Takasaki, Yoshinari; Yamamoto, Kazuhiko; Ikeuchi, Satoshi; Kushimoto, Satoru; Koike, Takao

2018-04-27

We evaluated the long-term (52 weeks) safety and effectiveness of iguratimod (IGU) in patients with rheumatoid arthritis (RA). This multicenter, prospective, observational study included all evaluable RA patients who received IGU since its market launch in 2012. We evaluated adverse events (AEs); adverse drug reactions (ADRs); ADRs of special interest, including liver and renal dysfunctions, interstitial lung disease, gastrointestinal and blood disorders, and infection; and change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) at week 52. Safety and effectiveness were analyzed in 2666 and 1614 patients, respectively. The incidences of AEs, serious AEs, ADRs, and serious ADRs were 46.92, 7.35, 38.26, and 4.58%, respectively. The incidence of ADRs peaked at approximately 4 weeks of treatment. Subsequently, the ADR incidence did not increase over time. Improvement of RA activity was shown up to week 52. Long-term treatment with IGU in patients with RA resulted in a tolerable safety profile and an improvement in RA activity. IGU could be considered a useful treatment option for patients with RA.

Effectiveness of occupational therapy in Parkinson's disease: study protocol for a randomized controlled trial.

PubMed

Sturkenboom, Ingrid H W M; Graff, Maud J; Borm, George F; Adang, Eddy M M; Nijhuis-van der Sanden, Maria W G; Bloem, Bastiaan R; Munneke, Marten

2013-02-02

Occupational therapists may have an added value in the care of patients with Parkinson's disease whose daily functioning is compromised, as well as for their immediate caregivers. Evidence for this added value is inconclusive due to a lack of rigorous studies. The aim of this trial is to evaluate the (cost) effectiveness of occupational therapy in improving daily functioning of patients with Parkinson's disease. A multicenter, assessor-blinded, two-armed randomized controlled clinical trial will be conducted, with evaluations at three and six months. One hundred ninety-two home-dwelling patients with Parkinson's disease and with an occupational therapy indication will be assigned to the experimental group or to the control group (2:1). Patients and their caregivers in the experimental group will receive ten weeks of home-based occupational therapy according to recent Dutch guidelines. The intervention will be delivered by occupational therapists who have been specifically trained to treat patients according to these guidelines. Participants in the control group will not receive occupational therapy during the study period. The primary outcome for the patient is self-perceived daily functioning at three months, assessed with the Canadian Occupational Performance Measure. Secondary patient-related outcomes include: objective performance of daily activities, self-perceived satisfaction with performance in daily activities, participation, impact of fatigue, proactive coping skills, health-related quality of life, overall quality of life, health-related costs, and effectiveness at six months. All outcomes at the caregiver level will be secondary and will include self-perceived burden of care, objective burden of care, proactive coping skills, overall quality of life, and care-related costs. Effectiveness will be evaluated using a covariance analysis of the difference in outcome at three months. An economic evaluation from a societal perspective will be conducted, as well as a process evaluation. This is the first large-scale trial specifically evaluating occupational therapy in Parkinson's disease. It is expected to generate important new information about the possible added value of occupational therapy on daily functioning of patients with Parkinson's disease. Clinicaltrials.gov: NCT01336127.

Evaluation of the Activity of Lamivudine and Zidovudine against Ebola Virus.

PubMed

Cong, Yu; Dyall, Julie; Hart, Brit J; DeWald, Lisa Evans; Johnson, Joshua C; Postnikova, Elena; Zhou, Huanying; Gross, Robin; Rojas, Oscar; Alexander, Isis; Josleyn, Nicole; Zhang, Tengfei; Michelotti, Julia; Janosko, Krisztina; Glass, Pamela J; Flint, Mike; McMullan, Laura K; Spiropoulou, Christina F; Mierzwa, Tim; Guha, Rajarshi; Shinn, Paul; Michael, Sam; Klumpp-Thomas, Carleen; McKnight, Crystal; Thomas, Craig; Eakin, Ann E; O'Loughlin, Kathleen G; Green, Carol E; Catz, Paul; Mirsalis, Jon C; Honko, Anna N; Olinger, Gene G; Bennett, Richard S; Holbrook, Michael R; Hensley, Lisa E; Jahrling, Peter B

2016-01-01

In the fall of 2014, an international news agency reported that patients suffering from Ebola virus disease (EVD) in Liberia were treated successfully with lamivudine, an antiviral drug used to treat human immunodeficiency virus-1 and hepatitis B virus infections. According to the report, 13 out of 15 patients treated with lamivudine survived and were declared free from Ebola virus disease. In this study, the anti-Ebola virus (EBOV) activity of lamivudine and another antiretroviral, zidovudine, were evaluated in a diverse set of cell lines against two variants of wild-type EBOV. Variable assay parameters were assessed to include different multiplicities of infection, lengths of inoculation times, and durations of dosing. At a multiplicity of infection of 1, lamivudine and zidovudine had no effect on EBOV propagation in Vero E6, Hep G2, or HeLa cells, or in primary human monocyte-derived macrophages. At a multiplicity of infection of 0.1, zidovudine demonstrated limited anti-EBOV activity in Huh 7 cells. Under certain conditions, lamivudine had low anti-EBOV activity at the maximum concentration tested (320 μM). However, lamivudine never achieved greater than 30% viral inhibition, and the activity was not consistently reproducible. Combination of lamivudine and zidovudine showed no synergistic antiviral activity. Independently, a set of in vitro experiments testing lamivudine and zidovudine for antiviral activity against an Ebola-enhanced green fluorescent protein reporter virus was performed at the Centers for Disease Control and Prevention. No antiviral activity was observed for either compound. A study evaluating the efficacy of lamivudine in a guinea pig model of EVD found no survival benefit. This lack of benefit was observed despite plasma lamivudine concentrations in guinea pig of about 4 μg/ml obtained in a separately conducted pharmacokinetics study. These studies found no evidence to support the therapeutic use of lamivudine for the treatment of EVD.

Associations between Viral Infection History Symptoms, Granulocyte Reactive Oxygen Species Activity, and Active Rheumatoid Arthritis Disease in Untreated Women at Onset: Results from a Longitudinal Cohort Study of Tatarstan Women

PubMed Central

Arleevskaya, Marina I.; Shafigullina, Albina Z.; Filina, Yulia V.; Lemerle, Julie; Renaudineau, Yves

2017-01-01

To evaluate the effects of infectious episodes at early stages of rheumatoid arthritis (eRA) development, 59 untreated eRA patients, 77 first-degree relatives, from a longitudinal Tatarstan women cohort, were included, and compared to 67 healthy women without rheumatoid arthritis (RA) in their family history. At inclusion, informations were collected regarding both the type and incidence of infectious symptom episodes in the preceding year, and granulocyte reactive oxygen species (ROS) were studied at the basal level and after stimulation with serum-treated zymosan (STZ). In the eRA group, clinical [disease activity score (DAS28), health assessment questionnaire] and biological parameters associated with inflammation (erythrocyte sedimentation rate, C-reactive protein) or with RA [rheumatoid factor, anticyclic citrullinated peptide (anti-CCP2) antibodies] were evaluated. An elevated incidence of infection events in the previous year characterized the eRA and relative groups. In addition, a history of herpes simplex virus (HSV) episodes was associated with disease activity, while an elevated incidence of anti-CCP2 autoantibody characterized eRA patients with a history of viral upper respiratory tract infection symptoms (V-URI). Granulocyte ROS activity in eRA patients was quantitatively [STZ peak and its area under the curve (AUC)] and qualitatively (STZ time of peak) altered, positively correlated with disease activity, and parameters were associated with viral symptoms including HSV exacerbation/recurrence, and V-URI. In conclusion, our study provides arguments to consider a history of increased viral infection symptoms in RA at the early stage and such involvement needs to be studied further. PMID:29259607

Associations between Viral Infection History Symptoms, Granulocyte Reactive Oxygen Species Activity, and Active Rheumatoid Arthritis Disease in Untreated Women at Onset: Results from a Longitudinal Cohort Study of Tatarstan Women.

PubMed

Arleevskaya, Marina I; Shafigullina, Albina Z; Filina, Yulia V; Lemerle, Julie; Renaudineau, Yves

2017-01-01

To evaluate the effects of infectious episodes at early stages of rheumatoid arthritis (eRA) development, 59 untreated eRA patients, 77 first-degree relatives, from a longitudinal Tatarstan women cohort, were included, and compared to 67 healthy women without rheumatoid arthritis (RA) in their family history. At inclusion, informations were collected regarding both the type and incidence of infectious symptom episodes in the preceding year, and granulocyte reactive oxygen species (ROS) were studied at the basal level and after stimulation with serum-treated zymosan (STZ). In the eRA group, clinical [disease activity score (DAS28), health assessment questionnaire] and biological parameters associated with inflammation (erythrocyte sedimentation rate, C-reactive protein) or with RA [rheumatoid factor, anticyclic citrullinated peptide (anti-CCP2) antibodies] were evaluated. An elevated incidence of infection events in the previous year characterized the eRA and relative groups. In addition, a history of herpes simplex virus (HSV) episodes was associated with disease activity, while an elevated incidence of anti-CCP2 autoantibody characterized eRA patients with a history of viral upper respiratory tract infection symptoms (V-URI). Granulocyte ROS activity in eRA patients was quantitatively [STZ peak and its area under the curve (AUC)] and qualitatively (STZ time of peak) altered, positively correlated with disease activity, and parameters were associated with viral symptoms including HSV exacerbation/recurrence, and V-URI. In conclusion, our study provides arguments to consider a history of increased viral infection symptoms in RA at the early stage and such involvement needs to be studied further.

Clinical significance of nailfold capillaroscopy in systemic lupus erythematosus: correlation with endothelial cell activation markers and disease activity.

PubMed

Kuryliszyn-Moskal, A; Ciolkiewicz, M; Klimiuk, P A; Sierakowski, S

2009-01-01

To evaluate whether nailfold capillaroscopy (NC) changes are associated with the main serum endothelial cell activation markers and the disease activity of systemic lupus erythematosus (SLE). Serum levels of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble E-selectin (sE-selectin), and soluble thrombomodulin (sTM) were determined by an enzyme-linked immunosorbent assay (ELISA) in 80 SLE patients and 33 healthy controls. Nailfold capillary abnormalities were seen in 74 out of 80 (92.5%) SLE patients. A normal capillaroscopic pattern or mild changes were found in 33 (41.25%) and moderate/severe abnormalities in 47 (58.75%) of all SLE patients. In SLE patients a capillaroscopic score >1 was more frequently associated with the presence of internal organ involvement (p < 0.001) as well as with immunosuppressive therapy (p < 0.01). Significant differences were found in VEGF (p < 0.001), ET-1 (p < 0.001), sE-selectin (p < 0.01), and sTM (p < 0.001) serum concentrations between SLE patients with a capillaroscopic score > 1 and controls. SLE patients with severe/moderate capillaroscopic abnormalities showed significantly higher VEGF serum levels than patients with mild changes (p < 0.001). Moreover, there was a significant positive correlation between the severity of capillaroscopic changes and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (p < 0.005) as well as between capillaroscopic score and VEGF serum levels (p < 0.001). Our findings confirm the usefulness of NC as a non-invasive technique for the evaluation of microvascular involvement in SLE patients. A relationship between changes in NC, endothelial cell activation markers and clinical features of SLE suggest an important role for microvascular abnormalities in clinical manifestation of the disease.

Allergic rhinitis and its impact on work productivity in primary care practice and a comparison with other common diseases: The Cross-sectional study to evAluate work Productivity in allergic Rhinitis compared with other common dIseases (CAPRI) study

PubMed Central

de la Hoz Caballer, Belén; Rodríguez, Mercedes; Fraj, Juan; Cerecedo, Inmaculada; Antolín-Amérigo, Darío

2012-01-01

Background: Allergic rhinitis (AR) is a highly prevalent allergic disease and also counts among the 10 most frequent reasons for medical consultation. Its impact on quality of life (QoL) and work productivity has been established but comparisons with other diseases are rare in the literature. The aim of this study was to evaluate the impact of AR in health-related QoL (HRQoL) and work productivity in primary care patients, compared with other prevalent diseases such as hypertension, diabetes mellitus (DM) type II, and symptomatic depression. Methods: Six hundred sixteen patients were included in a multicenter cross-sectional observational study. A generic HRQoL questionnaire, 36-item Short Form, and a specific questionnaire, “Work Productivity and Activity Impairment” were handed out to measure QoL and work productivity impact of the diseases. To assess clinical severity with a comparable scale between diseases Clinical Global Impression (CGI) had been used. Results: Symptomatic depression was found to produce the greatest impairment on work productivity with a decrease of 59.5%, with significant differences compared with AR, hypertension, and DM type II (p < 0.05). Symptomatic depression was found to produce the highest negative impact on daily activities with a statistically significant reduction of 59.4% (p < 0.05) compared with AR (26.6% decrease), hypertension (8.8% decrease), and DM (16.7% decrease) patients. Differences between AR and DM or hypertension were also significant (p < 0.05). Restriction on daily activities for AR was 27.8%, which is significantly higher (p < 0.05) than hypertension (19.8% decrease) but not DM (25.7% decrease). Depression had the highest impairment on daily activities (59.4%), compared with the remaining three groups (p < 0.05). Conclusion: AR impairs work productivity in a greater magnitude than hypertension and DM type II. PMID:23168153

Allergic rhinitis and its impact on work productivity in primary care practice and a comparison with other common diseases: the Cross-sectional study to evAluate work Productivity in allergic Rhinitis compared with other common dIseases (CAPRI) study.

PubMed

de la Hoz Caballer, Belén; Rodríguez, Mercedes; Fraj, Juan; Cerecedo, Inmaculada; Antolín-Amérigo, Darío; Colás, Carlos

2012-01-01

Allergic rhinitis (AR) is a highly prevalent allergic disease and also counts among the 10 most frequent reasons for medical consultation. Its impact on quality of life (QoL) and work productivity has been established but comparisons with other diseases are rare in the literature. The aim of this study was to evaluate the impact of AR in health-related QoL (HRQoL) and work productivity in primary care patients, compared with other prevalent diseases such as hypertension, diabetes mellitus (DM) type II, and symptomatic depression. Six hundred sixteen patients were included in a multicenter cross-sectional observational study. A generic HRQoL questionnaire, 36-item Short Form, and a specific questionnaire, "Work Productivity and Activity Impairment" were handed out to measure QoL and work productivity impact of the diseases. To assess clinical severity with a comparable scale between diseases Clinical Global Impression (CGI) had been used. Symptomatic depression was found to produce the greatest impairment on work productivity with a decrease of 59.5%, with significant differences compared with AR, hypertension, and DM type II (p < 0.05). Symptomatic depression was found to produce the highest negative impact on daily activities with a statistically significant reduction of 59.4% (p < 0.05) compared with AR (26.6% decrease), hypertension (8.8% decrease), and DM (16.7% decrease) patients. Differences between AR and DM or hypertension were also significant (p < 0.05). Restriction on daily activities for AR was 27.8%, which is significantly higher (p < 0.05) than hypertension (19.8% decrease) but not DM (25.7% decrease). Depression had the highest impairment on daily activities (59.4%), compared with the remaining three groups (p < 0.05). AR impairs work productivity in a greater magnitude than hypertension and DM type II.

Does physical activity affect quality of life, disease symptoms and immune measures in patients with inflammatory bowel disease? A systematic review.

PubMed

Packer, N; Hoffman-Goetz, L; Ward, G

2010-03-01

Inflammatory bowel diseases (IBD) are a group of chronic, episodic inflammatory conditions of the large and small intestines. Individuals with IBD have been reported to use physical activity (PA) as a complementary therapy although the effectiveness of PA for reducing disease burden in patients with IBD is not known. The review objective is to evaluate published studies on physical activity and IBD focusing on quality of life, disease burden markers and immunological outcomes. A literature search was carried out using MEDLINE, WEB OF SCIENCE, CINHAL, and SCOPUS (to December 2008). Studies were included if they 1) were provided in English; 2) dealt with IBD in humans; 3) focused on the outcome measures of health related quality of life, clinical disease indicators or immune function; and 4) included PA as a primary intervention for IBD cases. In total, 7 studies were included in this systematic review: 5 were on PA and quality of life measures and inflammatory disease markers, and 2 on PA and immune measures. Four studies showed that PA significantly increased quality of life for IBD patients as assessed by various questionnaires. PA was also associated with decreased disease activity. There was no evidence that PA affected immune outcomes in patients with IBD. The role of PA as an adjunctive therapy for patients with IBD has not been well characterized in the literature. However, there is some evidence that PA may improve quality of life and reduce disease activity in patients with IBD.

Cardiovascular effects of variations in habitual levels of physical activity

NASA Technical Reports Server (NTRS)

Blomqvist, C. G.; Mitchell, J. H.

1975-01-01

Mechanisms involved in human cardiovascular adaption to stress, particularly adaption to different levels of physical activity are determined along with quantitative noninvasive methods for evaluation of cardiovascular function during stess in normal subjects and in individuals with latent or manifest cardiovascular disease. Results are summarized.

Methodological issues in the design of a rheumatoid arthritis activity score and its cut-offs.

PubMed

Collignon, Olivier

2014-01-01

Activity of rheumatoid arthritis (RA) can be evaluated using several scoring scales based on clinical features. The most widely used one is the Disease Activity Score involving 28 joint counts (DAS28) for which cut-offs were proposed to help physicians classify patients. However, inaccurate scoring can lead to inappropriate medical decisions. In this article some methodological issues in the design of such a score and its cut-offs are highlighted in order to further propose a strategy to overcome them. As long as the issues reviewed in this article are not addressed, results of studies based on standard disease activity scores such as DAS28 should be considered with caution.

Proteomic profiling of eccrine sweat reveals its potential as a diagnostic biofluid for active tuberculosis.

PubMed

Adewole, Olanisun Olufemi; Erhabor, Greg Efosa; Adewole, Temitayo Oluwatoyin; Ojo, Abiodun Oluwasesan; Oshokoya, Harriet; Wolfe, Lisa M; Prenni, Jessica E

2016-05-01

Excessive sweating is a common symptom of the disease and an unexplored biofluid for TB diagnosis; we conducted a proof-of-concept study to identify potential diagnostic biomarkers of active TB in eccrine sweat. We performed a global proteomic profile of eccrine sweat sampled from patients with active pulmonary TB, other lung diseases (non-TB disease), and healthy controls. A comparison of proteomics between Active-TB, Non-TB, and Healthy Controls was done in search for potential biomarkers of active TB. Sweat specimens were pooled from 32 active TB patients, 27 patients with non-TB diseases, and 24 apparently healthy controls, all were negative for HIV. Over 100 unique proteins were identified in the eccrine sweat of all three groups. Twenty-six proteins were exclusively detected in the sweat of patients with active TB while the remaining detected proteins overlapped between three groups. Gene ontology evaluation indicated that the proteins detected uniquely in sweat of active TB patients were involved in immune response and auxiliary protein transport. Gene products for cellular components (e.g. ribosomes) were detected only in active TB patients. Data are available via ProteomeXchange with identifier PXD003224. Proteomics of sweat from active TB patients is a viable approach for biomarker identification, which could be used to develop a nonsputum-based test for detection of active TB. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Meteorological conditions and sports deaths at school in Japan, 1993 1998

NASA Astrophysics Data System (ADS)

Hoshi, Akio; Inaba, Yutaka

2005-03-01

We evaluated the association between meteorological conditions and sports deaths at elementary, junior high and senior high schools. Data were collected from attached documents such as accident reports and death certificate records in the National Agency for the Advancement of Sports and Health in Japan. Evaluation of seasonal variation showed a significant concentration of deaths from heat disorders and drowning in July and August. When heart disease was evaluated according to the sports situation, significant seasonal variation with a high number of deaths in September December was observed in sports events. Concerning circadian variation, deaths from heart disease showed a high peak at 10:00 11:00 a.m. in physical education classes and sports events, and at 2:00 5:00 p.m. in sports club activities. Analysis using a multiple logistic model showed a significantly lower odds ratio from heart disease and a significantly higher odds ratio from heat disorders at a wet bulb globe temperature of ≥21.0°C than at <21.0°C. According to the sports situation in heart disease, the odds ratio in sports club activities was significantly lower on days with rainfall than on days without rainfall. According to the school categories in heart diseases, the odds ratio in girls in elementary school was significantly higher than that in boys, but the odds ratio in girls in senior high school was significantly lower than that in boys.

IFN-γ, CXCL16, uPAR: potential biomarkers for systemic lupus erythematosus.

PubMed

Wen, Si; He, Fang; Zhu, Xuejing; Yuan, Shuguang; Liu, Hong; Sun, Lin

2018-01-01

IFN-γ, CXCL16 and uPAR have recently been regarded as potential biomarkers in systemic lupus erythematosus (SLE). However, few researches have focused on the comparison of these three markers in SLE. We conducted this study to evaluate their role as biomarkers of disease activity and renal damage. We enrolled 50 SLE patients with or without lupus nephritis (LN) and 15 healthy control subjects. The levels of IFN-γ, CXCL16, uPAR in serum, urine and renal tissues were detected by ELISA or immunohistochemistry. Relevant clinical and laboratory features were recorded. Serum and urine IFN-γ, CXCL16 and suPAR levels in SLE patients were significantly higher than that in healthy controls. Moreover, LN patients had higher levels than non-LN patients. A positive correlation was observed between these markers, and disease activity and suPAR had a stronger association with disease activity. The expression of these biomarkers in renal tissues was significantly higher in LN patients and was also associated with the activity of pathological lesions. IFN-γ, CXCL16 and uPAR are promising as effective biomarkers of disease activity, renal damage, and the activity of pathological lesions in SLE.

Assessment of antimalarial activity against Plasmodium falciparum and phytochemical screening of some Yemeni medicinal plants

PubMed Central

Alshawsh, Mohammed A.; Al-shamahy, Hassan A.; Alsllami, Salah F.; Lindequist, Ulrike

2009-01-01

Developing countries, where malaria is one of the most prevalent diseases, still rely on traditional medicine as a source for the treatment of this disease. In the present study, six selected plants (Acalypha fruticosa, Azadirachta indica, Cissus rotundifolia, Echium rauwalfii, Dendrosicyos socotrana and Boswellia elongata) commonly used in Yemen by traditional healers for the treatment of malaria as well as other diseases, were collected from different localities of Yemen, dried and extracted with methanol and water successfully. The antiplasmodial activity of the extracts was evaluated against fresh clinical isolates of Plasmodium falciparum. The selectivity parameters to evaluate the efficacy of these medicinal plants were measured by in vitro micro test (Mark III) according to World Health Organization (WHO) 1996 & WHO 2001 protocols of antimalarial drug tests. Among the investigated 12 extracts, three were found to have significant antiplasmodial activity with IC50 values less than 4 µg/ml, namely the water extracts of A. fruticosa, A. indica and D. socotrana. Six extracts showed moderate activity with IC50 values ranging from 10 to 30 µg/ml and three appeared to be inactive with IC50 values more than 30 µg/ml. In addition, preliminary phytochemical screening of the methanolic and aqueous extracts indicated the presence of saponins, tannins, flavonoids, terpenoids, polysaccharides and peptides. PMID:18955251

Correlation between Epstein-Barr Virus Infection and Disease Activity of Systemic Lupus Erythematosus: a Cross-Sectional Study

PubMed

Piroozmand, Ahmad; Haddad Kashani, Hamed; Zamani, Batool

2017-02-01

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease for whose pathogenesis viral infections are important. The Epstein-Barr virus (EBV) is the main infectious etiological agent. This study aimed to quantitative evaluation of EBV in SLE patients. Materials and Methods: In this cross-sectional study, 40 patients with SLE diagnosed based on American College of Rheumatology criteria were selected using purposive sampling. All were included in the study after obtaining informed consent for participation. Whole blood samples were taken and buffy coat preparations were isolated to determine viral load using the real-time polymerase chain reaction method and assessment with the SLE disease activity index (SLE-DAI). Results: From a total of 40 patients, 37 cases (92.5%) were women. The EBV test was positive in 67.5% and mean viral load was 5396 ± 1891.9 copy/ml. Twenty of forty patients had active and 50% inactive disease, mean EBV viral loads being 6798 and 28.25 copy/ml, respectively (P-value = 0.003). In terms of the severity of disease activity, 17.5 % of female patients had mild to moderate activity, whilst 32.5% of them had severe activity, with respective viral loads of 5,803.3 and 29.73 copy/ml (P-value = 0.003). Conclusion: The Epstein-Barr viral load in SLE patients with active disease was found to be markedly higher than in inactive cases. Thus, EBV may have an important role in the pathogenesis and activity of SLE. Creative Commons Attribution License

Quantitative Evaluation of the Use of Actigraphy for Neurological and Psychiatric Disorders

PubMed Central

Song, Yu; Kwak, Shin; Yoshida, Sohei; Yamamoto, Yoshiharu

2014-01-01

Quantitative and objective evaluation of disease severity and/or drug effect is necessary in clinical practice. Wearable accelerometers such as an actigraph enable long-term recording of a patient's movement during activities and they can be used for quantitative assessment of symptoms due to various diseases. We reviewed some applications of actigraphy with analytical methods that are sufficiently sensitive and reliable to determine the severity of diseases and disorders such as motor and nonmotor disorders like Parkinson's disease, sleep disorders, depression, behavioral and psychological symptoms of dementia (BPSD) for vascular dementia (VD), seasonal affective disorder (SAD), and stroke, as well as the effects of drugs used to treat them. We believe it is possible to develop analytical methods to assess more neurological or psychopathic disorders using actigraphy records. PMID:25214709

Effects of Achieving Target Measures in Rheumatoid Arthritis on Functional Status, Quality of Life, and Resource Utilization: Analysis of Clinical Practice Data.

PubMed

Alemao, Evo; Joo, Seongjung; Kawabata, Hugh; Al, Maiwenn J; Allison, Paul D; Rutten-van Mölken, Maureen P M H; Frits, Michelle L; Iannaccone, Christine K; Shadick, Nancy A; Weinblatt, Michael E

2016-03-01

To evaluate associations between achieving guideline-recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) <2.6, the Simplified Disease Activity Index (SDAI) ≤3.3, or the Clinical Disease Activity Index (CDAI) ≤2.8, and other health outcomes in a longitudinal observational study. Other defined thresholds included low disease activity (LDA), moderate (MDA), or severe disease activity (SDA). To control for intraclass correlation and estimate effects of independent variables on outcomes of the modified Health Assessment Questionnaire (M-HAQ), the EuroQol 5-domain (EQ-5D; a quality-of-life measure), hospitalization, and durable medical equipment (DME) use, we employed mixed models for continuous outcomes and generalized estimating equations for binary outcomes. Among 1,297 subjects, achievement (versus nonachievement) of recommended disease targets was associated with enhanced physical functioning and lower health resource utilization. After controlling for baseline covariates, achievement of disease targets (versus LDA) was associated with significantly enhanced physical functioning based on SDAI ≤3.3 (ΔM-HAQ -0.047; P = 0.0100) and CDAI ≤2.8 (-0.073; P = 0.0003) but not DAS28-CRP <2.6 (-0.022; P = 0.1735). Target attainment was associated with significantly improved EQ-5D (0.022-0.096; P < 0.0030 versus LDA, MDA, or SDA). Patients achieving guideline-recommended disease targets were 36-45% less likely to be hospitalized (P < 0.0500) and 23-45% less likely to utilize DME (P < 0.0100). Attaining recommended target disease-activity measures was associated with enhanced physical functioning and health-related quality of life. Some health outcomes were similar in subjects attaining guideline targets versus LDA. Achieving LDA is a worthy clinical objective in some patients. © 2016 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Clinical Value of FDG-PET/CT for the Evaluation of Rheumatic Diseases: Rheumatoid Arthritis, Polymyalgia Rheumatica, and Relapsing Polychondritis.

PubMed

Kubota, Kazuo; Yamashita, Hiroyuki; Mimori, Akio

2017-07-01

FDG is a tracer for visualizing glucose metabolism. PET/CT using FDG is widely used for the diagnosis of cancer, because glycolysis is elevated in cancer cells. Similarly, active inflammatory tissue also exhibits elevated glucose metabolism because of glycolysis in activated macrophages and proliferating fibroblasts. Elevated FDG uptake by active inflammatory tissues, such as those affected by arthritis, vasculitis, lymphadenitis, and chondritis, has enabled the diagnosis of inflammatory diseases using FDG-PET/CT. Rheumatoid arthritis (RA) is a systemic, chronic inflammation of the joints resulting in synovitis. Several clinical studies of RA have demonstrated that FDG uptake in affected joints reflects the disease activity of RA, with strong correlations between FDG uptake and various clinical parameters having been noted. Furthermore, the use of FDG-PET for the sensitive detection and early monitoring of the response to RA therapy has been reported. RA is sometimes associated with subclinical vasculitis, which is related to systemic inflammation. FDG-PET/CT can be used to evaluate subclinical vasculitis in the aorta or carotid artery. Polymyalgia rheumatica (PMR) is an autoimmune musculoskeletal disease of unknown etiology characterized by pain and stiffness in the shoulder, neck, and pelvic girdle, but not in the small finger joints in the hands, together with fever, fatigue, and weight loss. There is no specific test for PMR, and its diagnosis is based on clinical diagnostic criteria and the exclusion of other diseases with similar symptoms. However, FDG-PET/CT reveals a characteristic FDG uptake by the bursitis in ischial tuberosity, greater trochanter, lumbar or cervical spinous process, and scapulohumeral joint. A combination of FDG-PET/CT findings showed a high diagnostic value for PMR in a differential diagnosis from RA. FDG-PET/CT is also very useful for evaluating large vessel vasculitis, which is often associated with PMR. Relapsing polychondritis is a rare multisystem disease of unknown etiology involving cartilaginous and proteoglycan-rich structures. Its rarity and diversity of symptoms often result in a delayed diagnosis. FDG-PET/CT reveals unique FDG uptake findings for chondritis in the auricular, nasal, trachea, bronchial tree, and costal cartilage and in the cartilage of joints. Thus, the spread of knowledge regarding these very specific FDG-PET/CT findings could promote the early diagnosis and improved disease control of relapsing polychondritis. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuromuscular rate of force development deficit in Parkinson disease.

PubMed

Hammond, Kelley G; Pfeiffer, Ronald F; LeDoux, Mark S; Schilling, Brian K

2017-06-01

Bradykinesia and reduced neuromuscular force exist in Parkinson disease. The interpolated twitch technique has been used to evaluate central versus peripheral manifestations of neuromuscular strength in healthy, aging, and athletic populations, as well as moderate to advanced Parkinson disease, but this method has not been used in mild Parkinson disease. This study aimed to evaluate quadriceps femoris rate of force development and quantify potential central and peripheral activation deficits in individuals with Parkinson disease. Nine persons with mild Parkinson Disease (Hoehn & Yahr≤2, Unified Parkinson Disease Rating Scale total score=mean 19.1 (SD 5.0)) and eight age-matched controls were recruited in a cross-sectional investigation. Quadriceps femoris voluntary and stimulated maximal force and rate of force development were evaluated using the interpolated twitch technique. Thirteen participants satisfactorily completed the protocol. Individuals with early Parkinson disease (n=7) had significantly slower voluntary rate of force development (p=0.008; d=1.97) and rate of force development ratio (p=0.004; d=2.18) than controls (n=6). No significant differences were found between groups for all other variables. Persons with mild-to-moderate Parkinson disease display disparities in rate of force development, even without deficits in maximal force. The inability to produce force at a rate comparable to controls is likely a downstream effect of central dysfunction of the motor pathway in Parkinson disease. Copyright © 2017. Published by Elsevier Ltd.

Occurrence of oxidative stress in dairy cows seropositives for Brucella abortus.

PubMed

Perin, Géssica; Fávero, Juscivete F; Severo, Diego R T; Silva, Anielen D; Machado, Gustavo; Araújo, Hugo L; Lilenbaum, Walter; Morsch, Vera M; Schetinger, Maria Rosa C; Jordão, Ricardo S; Stefani, Lenita M; Bottari, Nathieli B; Da Silva, Aleksandro S

2017-09-01

Bovine brucellosis is an important zoonotic disease caused by the bacterium Brucella abortus that leads to economic losses due to animal discard and commercial restrictions. Since positive animals for brucellosis are culled, little is known about the pathogenesis of this disease. Therefore, the aims of this study were to evaluate possible changes in the activity of deaminase adenosine (ADA) and the oxidative stress in cows seropositives for brucellosis (Experiment I), and to evaluate the seroprevalence of B. abortus in dairy cows from the Western state of Santa Catarina, Southern Brazil (Experiment II). The Experiment I evaluated 20 pregnant cows: ten seropositives for B. abortus and ten seronegatives that were used as controls. The ADA activity and markers of oxidative stress (TBARS, catalase (CAT) and superoxide dismutase (SOD)) were evaluated in these animals. A reduction in the activity of ADA and catalase enzymes in seropositive animals was observed (p < 0.001). Conversely, there was an increase in TBARS levels and superoxide dismutase activity in cows infected by B. abortus (p < 0.001). The presence of oxidative stress and a reduction of ADA might be related to the modulation of the inflammatory response. The experiment II was performed due to a high number of herds with restrictions imposed by cases of brucellosis in the state of Santa Catarina in the last two years, and thus, the seroprevalence for B. abortus was evaluated in 1242 serum samples of cows of 69 herds. The serodiagnosis was performed using two tests: buffered acidified antigen and 2-mercaptoethanol. However, none of the serum samples were positive for B. abortus. Although we did not find seropositive animals for brucellosis in our study, the disease still requires continued surveillance, due to its economic impact, and to the oxidative stress caused by it, which may have contributed to cases of abortion in three seropositive cows (Experiment I) in the final third of the gestation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of disease modifying activity of Coriandrum sativum in experimental models

PubMed Central

Nair, Vinod; Singh, Surender; Gupta, Y.K.

2012-01-01

Background & objectives: Coriandrum sativum (CS), has been widely used in traditional systems of medicine for treatment of rheumatoid arthritis. However, the mechanism of action for its antiarthritic effects is not clearly known. Therefore, the present study was carried out to evaluate the antiarthritic activity of CS in rats in two experimental models. Methods: The antiarthritic activity of CS seed hydroalcoholic extract (CSHE) was evaluated in adult Wistar rats by using two experimental models, viz. formaldehyde and Complete Freund's adjuvant (CFA) induced arthritis. The expression of pro-inflammatory cytokines (predominantly contributed by macrophages) was also evaluated. TNF-α level was estimated in serum by ELISA method. TNF-R1, IL-1 β and IL-6 expression in the synovium was analysed by immunohistochemistry. Results: CSHE produced a dose dependent inhibition of joint swelling as compared to control animals in both, formaldehyde and CFA induced arthritis. Although there was a dose dependent increase in serum TNF-α levels in the CSHE treated groups as compared to control, the synovial expression of macrophage derived pro-inflammatory cytokines/cytokine receptor was found to be lower in the CSHE treated groups as compared to control. Interpretation & conclusions: Our results demonstrate that the antiarthritic activity of CSHE may be attributed to the modulation of pro-inflammatory cytokines in the synovium. In further studies CSHE could be explored to be developed as a disease modifying agent in the treatment of RA. PMID:22446868

Milk thistle and its derivative compounds: a review of opportunities for treatment of liver disease.

PubMed

Hackett, E S; Twedt, D C; Gustafson, D L

2013-01-01

Milk thistle extracts have been used as a "liver tonic" for centuries. In recent years, silibinin, the active ingredient in milk thistle extracts, has been studied both in vitro and in vivo to evaluate the beneficial effects in hepatic disease. Silibinin increases antioxidant concentrations and improves outcomes in hepatic diseases resulting from oxidant injury. Silibinin treatment has been associated with protection against hepatic toxins, and also has resulted in decreased hepatic inflammation and fibrosis. Limited information currently is available regarding silibinin use in veterinary medicine. Future study is justified to evaluate dose, kinetics, and treatment effects in domestic animals. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Evaluation of the Usability of Selected Questionnaires Assessing Physical Activity in the Prophylaxis of Cardiovascular Diseases.

PubMed

Czeczelewska, Ewa; Czeczelewski, Jan; Wasiluk, Agnieszka; Saczuk, Jerzy

2016-01-01

The main health problem of the Polish population is posed by cardiovascular diseases (CDVD), coronary artery disease (CAD) in particular. Respectively higher physical activity linked with energy expenditure of at least 1000 kcal/week may significantly reduce the risk of CAD development. The protective effect of exercise applies not only to persons from high-risk groups and with diagnosed chronic diseases that increase the risk of the incidence of atherosclerosis and its complications, but also to healthy individuals. The aim of this study was to evaluate the usability of the Seven-Day Physical Activity Recall (SDPAR) and International Physical Activity Questionnaire (IPAQ) in research on the correlation between physical activity and risk factors of cardiovascular diseases. A screening survey, conducted in 2012, included students (n = 340) of the Division of the Academy of Physical Education in Biała Podlaska, aged 18-29 years. Total cholesterol, triglycerides and glucose levels were analyzed, and arterial blood pressure and heart rate were measured. The physical activity of the students was estimated using IPAQ and SDPAR questionnaires. The effect of physical activity on the biochemical blood markers, arterial blood pressure and heart rate was analyzed in groups differing in weekly energy expenditure (WEE). Along with increasing WEE values, calculated with IPAQ and SDPAR questionnaires, tangible descending tendencies were observed in cholesterol concentration in both genders. Significant differences were demonstrated in mean values of the resting heart rate between terciles of women ranked according to the increasing WEE values calculated using IPAQ (p < 0.05) and SDPAR (p < 0.01). Significant (p < 0.05) negative correlations were demonstrated only between the heart rate of women and WEE value calculated with IPAQ (r = -0.223) and SDPAR (r = -0.238). Beneficial changes were observed in the blood lipid profile and in mean resting heart rate values as affected by the higher energy expenditure. The IPAQ and SDPAR may be applied to assess the level of physical activity; however the SDPAR seems to be a more useful tool in CDVD prevention screening.

Therapeutic evaluation of GM2 gangliosidoses by ELISA using anti-GM2 ganglioside antibodies.

PubMed

Tsuji, Daisuke; Higashine, Yukari; Matsuoka, Kazuhiko; Sakuraba, Hitoshi; Itoh, Kohji

2007-03-01

GM2 gangliosidoses, including Tay-Sachs disease, Sandhoff disease and the AB variant, comprise deficiencies of beta-hexosaminidase isozymes and GM2 ganglioside activator protein associated with accumulation of GM2 ganglioside (GM2) in lysosomes and neurosomatic clinical manifestations. A simple assay system for intracellular quantification of GM2 is required to evaluate the therapeutic effects on GM2-gangliosidoses. We newly established a cell-ELISA system involving anti-GM2 monoclonal antibodies for measuring GM2 storage in fibroblasts from Tay-Sachs and Sandhoff disease patients. We succeeded in detecting the corrective effect of enzyme replacement on elimination of GM2 in the cells with this ELISA system. This simple and sensitive system should be useful as additional diagnosis tool as well as therapeutic evaluation of GM2 gangliosidoses.

International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies.

PubMed

Bentow, C; Lakos, G; Martis, P; Wahl, E; Garcia, M; Viñas, O; Espinosa, G; Cervera, R; Sjöwall, C; Carmona-Fernandes, D; Santos, M J; Hanly, J G; Mahler, M

2016-07-01

Anti-double stranded desoxyribonucleic acid (anti-dsDNA) antibodies are considered fairly specific for systemic lupus erythematosus (SLE) and their quantification is useful for the clinical management of SLE patients. We assessed the diagnostic performance of the QUANTA Flash dsDNA chemiluminescent immunoassay (CIA) in comparison to an ELISA, using patients from five participating countries. The main focus was to evaluate the correlation between anti-dsDNA antibody results from the CIA and global SLE disease activity, as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). A total of 1431 samples (SLE, n = 843; disease controls, n = 588) from five countries (Canada, USA, Portugal, Sweden and Spain) were tested with QUANTA Flash dsDNA (Inova Diagnostics, San Diego, CA, USA). Data obtained with the QUANTA Lite dsDNA SC ELISA (Inova Diagnostics) were available for samples from three sites (Canada, USA and Sweden, n = 566). The SLEDAI-2K scores were available for 805 SLE patients and a cut-off of > 4 was used to define active disease. QUANTA Flash dsDNA had a sensitivity of 54.3% for the diagnosis of SLE, combined with 89.8% specificity. Anti-dsDNA antibody levels were significantly higher (p < 0.0001) in active SLE (SLEDAI-2K > 4; n = 232; median value 83.0 IU/mL) versus the inactive patients (n = 573; median value 22.3 IU/mL), and the SLEDAI-2K scoring correlated with their dsDNA antibody levels (Spearman's rho = 0.44, p < 0.0001). Similar but less pronounced findings were also found for the ELISA, in relation to disease activity. The QUANTA Flash dsDNA assay showed good clinical performance in a large international multi-center study. Additionally, the strong correlation between anti-dsDNA antibody results and SLEDAI-2K scores supported the potential utility of QUANTA Flash dsDNA for monitoring disease activity. © The Author(s) 2016.

Employees on the Move!

ERIC Educational Resources Information Center

Levin, Sarah

This paper describes a method for designing, implementing, and evaluating a work-site physical activity campaign aimed at employees who are currently sedentary in their leisure time. Inactivity is a major but modifiable risk factor for coronary heart disease. Increasing the activity levels of underactive adults would have a positive impact on…

Synthesis and Biological Evaluation of Water-soluble Progesterone-Conjugated Probes for Magnetic Resonance Imaging of Hormone Related Cancers

PubMed Central

Sukerkar, Preeti A.; MacRenaris, Keith W.; Townsend, Taryn R.; Ahmed, Roshan A.; Burdette, Joanna E.; Meade, Thomas J.

2011-01-01

Progesterone receptor (PR) is strongly associated with disease prognosis and therapeutic efficacy in hormone related diseases such as endometriosis and breast, ovarian, and uterine cancers. Receptor status is currently determined by immunohistochemistry assays. However, noninvasive PR imaging agents could improve disease detection and help elucidate pathological molecular pathways, leading to new therapies and animal disease models. A series of water-soluble PR-targeted magnetic resonance imaging (MRI) probes were synthesized using Cu(I)-catalyzed click chemistry and evaluated in vitro and in vivo. These agents demonstrated activation of PR in vitro and preferential accumulation in PR(+) compared to PR(−) human breast cancer cells with low toxicity. In xenograft tumor models, the agents demonstrated enhanced signal intensity in PR(+) tumors compared to PR(−) tumors. The results suggest that these agents may be promising MRI probes for PR(+) diseases. PMID:21972997

Prognostic value of one-year course of symptoms of anxiety and depression in patients with coronary heart disease: Role of physical activity and unmet medical need.

PubMed

Rothenbacher, Dietrich; Jaensch, Andrea; Mons, Ute; Hahmann, Harry; Becker, Thomas; Koenig, Wolfgang; Brenner, Hermann

2015-09-01

Symptoms of depression and anxiety contribute to determining prognosis of patients with coronary heart disease. We evaluated the association of the one-year course of symptoms of anxiety and depressive symptoms with fatal and non-fatal cardiovascular disease-events during 10-year follow-up and assessed the utilization of anti-depressant and psycholeptic medication. Prospective cohort study in coronary heart disease patients aged 30-70 years with stable coronary heart disease. Symptoms of anxiety and depression were evaluated at baseline and follow-up using the Hospital Anxiety and Depression Scale. Associations with fatal and non-fatal cardiovascular disease events were determined by a Cox-proportional hazards model. Nine hundred and ninety-six patients were included in this study. Of the 862 patients with a normal depression symptom score at baseline 10.3% had an increased score at one-year follow-up. Of those with an elevated symptom score at baseline, 62.7% still had an elevated score after one year. During follow-up (median 8.9 years) fatal and non-fatal cardiovascular disease events were observed in 152 patients. One year course of depressive symptoms was associated with cardiovascular disease events during follow-up (p-value for trend 0.029); for example, patients with an increase of depressive symptoms had a hazard ratio of 1.93 (95% confidence interval 1.08-3.34) compared with patients with a normal score at baseline as well as at one-year follow-up. However, if physical activity was considered as a covariate, the HRs attenuated and the association was no longer statistically significant. The utilization of anti-depressant medication in the overall population was low (overall 2%). The study supports a role of the one year course of symptoms of depression for long-term prognosis of patients with known coronary heart disease, which might be partly mediated by lack of physical activity. © The European Society of Cardiology 2014.

The impact of a disease-management program on the symptom experience of older women with heart disease.

PubMed

Janz, N K; Clark, N M; Dodge, J A; Schork, M A; Mosca, L; Fingerlin, T E

1999-01-01

This study describes the symptom experience of 570 older women with heart disease and evaluates a disease-management program's impact on symptoms over time. Women were randomly assigned to either usual care or a 4-week program ("Women take PRIDE") designed to improve self-regulation skills by focusing on increasing physical activity. At 4 months follow-up, program women, compared to controls, reported fewer total symptoms (p = 0.01) and decreased symptom frequency (p = 0.02) and bothersomeness (p = 0.02). By 12 months, positive intervention effects emerged within the common cardiac and sleep and rest symptom categories. Program group women reported more improvements in symptoms likely to be affected by increasing physical activity at both follow-ups (p < 0.05).

A Randomized, Double-blind, Placebo-controlled Clinical Trial Examining the Effects of Green Tea Extract on Systemic Lupus Erythematosus Disease Activity and Quality of Life.

PubMed

Shamekhi, Z; Amani, R; Habibagahi, Z; Namjoyan, F; Ghadiri, Ata; Saki Malehi, A

2017-07-01

Antiinflammatory and immunomodulatory benefit of green tea (Camellia sinensis) in autoimmune disease has been proven in recent studies. The objective of this study was to assess the effects of green tea on disease activity and quality of life in systemic lupus erythematosus patients. A randomized controlled trial on subjects with lupus was conducted, and 68 patients in the age range of 39.1 ± 10.3 years and body mass index of 25.7 ± 5.21 kg/m 2 completed the 12-week study. Patients were randomly divided into two groups of intervention (1000 mg green tea extract, two capsules/day) and control (1000 mg of starch, two capsules/day). Main outcome measure, systemic lupus erythematosus disease activity, was assessed by the systemic lupus erythematosus disease activity index at the first and after 3 months of intervention. In addition, patient's quality of life was evaluated by short form of quality-of-life questionnaire at baseline and after 3 months. Green tea extract supplementation significantly reduced disease activity in lupus patients (p < 0.004); in addition, it significantly increased the vitality (p < 0.006) and general health (p < 0.01). This study showed that daily consumption of green tea extracts for 12 weeks improves the systemic lupus erythematosus disease activity as well as some aspects of quality of life. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma.

PubMed

Magee, Kelsey E; Kelsey, Christina E; Kurzinski, Katherine L; Ho, Jonhan; Mlakar, Logan R; Feghali-Bostwick, Carol A; Torok, Kathryn S

2013-01-01

The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures. The presence of IP-10 in the plasma was analyzed using a Luminex panel in 69 pediatric patients with LS and compared to 71 healthy pediatric controls. Of these patients, five had available skin biopsy specimens with concurrent clinical and serological data during the active disease phase, which were used to analyze the presence and location of IP-10 in the skin by immunohistochemistry (IHC). IP-10 levels were significantly elevated in the plasma of LS patients compared to that of healthy controls and correlated to clinical disease activity measures in LS. Immunohistochemistry staining of IP-10 was present in the dermal infiltrate of LS patients and was similar to that found in psoriasis skin specimens, the positive disease control. Elevation of IP-10 levels in the plasma compared to those of healthy controls and the presence of IP-10 staining in the affected skin of LS patients indicates that IP-10 is a potential biomarker in LS. Furthermore, significant elevation of IP-10 in LS patients with active versus inactive disease and correlations between IP-10 levels and standardized disease outcome measures of activity in LS strongly suggest that IP-10 may be a biomarker for disease activity in LS.

Autologous mesenchymal stem cell treatment increased T regulatory cells with no effect on disease activity in two systemic lupus erythematosus patients.

PubMed

Carrion, F; Nova, E; Ruiz, C; Diaz, F; Inostroza, C; Rojo, D; Mönckeberg, G; Figueroa, F E

2010-03-01

Mesenchymal stem cells (MSCs) exert suppressive effects in several disease models including lupus prone mice. However, autologous MSC therapy has not been tested in human systemic lupus erythematosus (SLE). We evaluate the safety and efficacy of bone marrow (BM)-derived MSCs in two SLE patients; the suppressor effect of these cells in-vitro and the change in CD4+CD25+FoxP3+ T regulatory (Treg) cells in response to treatment. Two females (JQ and SA) of 19 and 25 years of age, fulfilling the 1997 American College of Rheumatology (ACR) criteria for SLE were infused with autologous BM-derived MSCs. Disease activity indexes and immunological parameters were assessed at baseline, 1, 2, 7 and 14 weeks. Peripheral blood lymphocyte (PBL) subsets and Treg cells were quantitated by flow cytometry, and MSCs tested for in-vitro suppression of activation and proliferation of normal PBLs. No adverse effects or change in disease activity indexes were noted during 14 weeks of follow-up, although circulating Treg cells increased markedly. Patient MSCs effectively suppressed in-vitro PBL function. However, JQ developed overt renal disease 4 months after infusion. MSC infusion was without adverse effects, but did not modify initial disease activity in spite of increasing CD4+CD25+FoxP3+ cell counts. One patient subsequently had a renal flare. We speculate that the suppressive effects of MSC-induced Treg cells might be dependent on a more inflammatory milieu, becoming clinically evident in patients with higher degrees of disease activity.

Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma

PubMed Central

2013-01-01

Introduction The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures. Methods The presence of IP-10 in the plasma was analyzed using a Luminex panel in 69 pediatric patients with LS and compared to 71 healthy pediatric controls. Of these patients, five had available skin biopsy specimens with concurrent clinical and serological data during the active disease phase, which were used to analyze the presence and location of IP-10 in the skin by immunohistochemistry (IHC). Results IP-10 levels were significantly elevated in the plasma of LS patients compared to that of healthy controls and correlated to clinical disease activity measures in LS. Immunohistochemistry staining of IP-10 was present in the dermal infiltrate of LS patients and was similar to that found in psoriasis skin specimens, the positive disease control. Conclusions Elevation of IP-10 levels in the plasma compared to those of healthy controls and the presence of IP-10 staining in the affected skin of LS patients indicates that IP-10 is a potential biomarker in LS. Furthermore, significant elevation of IP-10 in LS patients with active versus inactive disease and correlations between IP-10 levels and standardized disease outcome measures of activity in LS strongly suggest that IP-10 may be a biomarker for disease activity in LS. PMID:24499523

Inflammatory myopathies in childhood: correlation between nailfold capillaroscopy findings and clinical and laboratory data.

PubMed

Nascif, Ana K S; Terreri, Maria T R A; Len, Cláudio A; Andrade, Luis E C; Hilário, Maria O E

2006-01-01

Nailfold capillaroscopy is an important tool for the diagnosis and follow-up of patients with rheumatic diseases, in particular dermatomyositis and scleroderma. A relationship has been observed in adults between improved capillaroscopic findings and reduced disease activity. Our aim was to correlate disease activity (clinical and laboratory data) and nailfold capillaroscopy findings in 18 patients with inflammatory myopathies. This prospective study included 13 juvenile dermatomyositis patients (Bohan and Peter criteria) (mean age of 8.8 years) and five patients with overlap syndrome (mean age of 15.7 years). We evaluated disease activity (skin abnormalities and muscle weakness, muscle enzymes and acute phase reactants) and its correlation with nailfold capillaroscopy findings (dilatation of isolated loops, dropout of surrounding vessels and giant capillary loops). We used a microscope with special light and magnification of 10 to 16X. Eighteen patients underwent a total of 26 capillaroscopic examinations, seven of them on two or more occasions (13 were performed during the active disease phase and 13 during remission). Twelve of the 13 examinations performed during the active phase exhibited scleroderma pattern and 8 of the 13 examinations performed during remission were normal. Therefore, in 20 of the 26 examinations clinical and laboratory data and nailfold capillaroscopy findings correlated (p = 0.01). Nailfold capillaroscopy is a non-invasive examination that offers satisfactory correlation with disease activity and could be a useful tool for the diagnosis and follow-up of inflammatory myopathies.

Targeting AMPK Signaling as a Neuroprotective Strategy in Parkinson's Disease.

PubMed

Curry, Daniel W; Stutz, Bernardo; Andrews, Zane B; Elsworth, John D

2018-03-26

Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is characterized by the accumulation of intracellular α-synuclein aggregates and the degeneration of nigrostriatal dopaminergic neurons. While no treatment strategy has been proven to slow or halt the progression of the disease, there is mounting evidence from preclinical PD models that activation of 5'-AMP-activated protein kinase (AMPK) may have broad neuroprotective effects. Numerous dietary supplements and pharmaceuticals (e.g., metformin) that increase AMPK activity are available for use in humans, but clinical studies of their effects in PD patients are limited. AMPK is an evolutionarily conserved serine/threonine kinase that is activated by falling energy levels and functions to restore cellular energy balance. However, in response to certain cellular stressors, AMPK activation may exacerbate neuronal atrophy and cell death. This review describes the regulation and functions of AMPK, evaluates the controversies in the field, and assesses the potential of targeting AMPK signaling as a neuroprotective treatment for PD.

Serum gamma-glutamyltransferase activity is increased in patients with calcific aortic valve stenosis.

PubMed

Bozbas, Huseyin; Yildirir, Aylin; Demir, Ozlem; Cakmak, Abdulkadir; Karacaglar, Emir; Yilmaz, Mustafa; Eroglu, Serpil; Pirat, Bahar; Ozin, Bulent; Muderrisoglu, Haldun

2008-07-01

A growing body of data indicates an independent association between serum gamma-glutamyltransferase (GGT) activity, a marker of increased oxidative stress, and cardiovascular diseases. The process of calcific aortic valve disease has been shown to present characteristics of atherosclerosis. The study aim was to evaluate the possible role of serum GGT in patients with calcific aortic valve disease. The results of patients' echocardiography studies from 2005 for the presence of calcific aortic valve disease in the forms of aortic stenosis (AS) and aortic valve calcification (AVC) without significant valve stenosis, were retrospectively evaluated. Age-and gender-matched patients with normal aortic valve morphology were selected at random as a control group. A total of 383 patients was enrolled into the study (126 with AS, 133 with AVC, 124 controls). Serum GGT activity, along with other liver enzyme analyses and laboratory results, were determined and compared among the groups. Age, gender and clinical and laboratory results were similar among the three groups. Median serum GGT levels in the AS, AVC and control groups were 23.0 U/1 (mean 31.5 +/- 24.9 U/1), 22.0 U/1 (mean 27.6 +/- 18.6 U/) and 18.0 U/l (mean 22.4 +/- 16.4 U/l), respectively. Compared to controls, AS patients had significantly higher serum GGT and C-reactive protein levels, while the differences between AVC patients and controls for these parameters were not significant. The study results suggest that serum GGT activity is increased in patients with calcific AS. These increases seem to occur in advanced rather than milder forms of calcific aortic valve disease.

Rheumatoid arthritis disease activity and disability affect the risk of serious infection events in RADIUS 1.

PubMed

Weaver, Arthur; Troum, Orrin; Hooper, Michele; Koenig, Andrew S; Chaudhari, Sandeep; Feng, Jingyuan; Wenkert, Deborah

2013-08-01

To determine whether disease activity and disability independently correlate with serious infection event (SIE) risk in a large rheumatoid arthritis (RA) cohort. The associations between SIE and Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in the Rheumatoid Arthritis Disease-Modifying Antirheumatic Drug Intervention and Utilization Study (RADIUS 1) cohort were evaluated using the Andersen-Gill model (a proportional HR model allowing > 1 event per patient). Of 4084 patients with 347 SIE, 271 patients experienced ≥ 1 SIE. A 5-unit CDAI increase and 0.4-unit HAQ-DI increase corresponded to an increase in SIE risk with and without covariate adjustments. A 5-unit CDAI increase corresponded with a 7.7% increased SIE risk (adjusted HR 1.077, 95% CI 1.044-1.112, p < 0.0001) and a 0.4-unit HAQ-DI increase with a 30.1% increased risk (adjusted HR 1.301, 95% CI 1.225-1.381, p < 0.0001). Categorical analysis showed that more severe RA activity (even after controlling for disability) and disability were associated with an increased SIE risk. Increased RA disease activity and disability were each associated with a significantly increased SIE risk in the RADIUS 1 cohort, which could not be completely accounted for by disability.

Depressive mood and disease activity in inflammatory bowel disease.

PubMed

Besharat, Sima; Amiriani, Taghi; Roshandel, Gholamreza; Besharat, Mahsa; Semnani, Shahryar; Kamkar, Mohammadzaman

2012-09-01

Some mood disorders are more prevalent in chronic medical conditions compared with the general population. The relationship between inflammatory bowel disease (IBD) and psychiatric disorders has been raised as an area of interest for investigation. In this study, we aimed to assess the probable relationship between depression and disease activity in IBD patients in Golestan province, northeast of Iran. During February 2008 to February 2010, 50 patients recently diagnosed as IBD cases attended the Golestan Research Center of Gastroenterology and Hepatology (GRCGH), northeast of Iran. The Simple Clinical Colitis Activity Index (SCCAI) was used to evaluate the disease activity. The Beck Depression Inventory (BDI) was used to assess the severity of depressive symptoms. Depression was assumed when the BDI score was 13 points or higher. Sixteen cases (32%) had depressive characteristics. SCCAI and the Beck score were not significantly different between the two sexes. There was a non-significant correlation between SCCAI, Beck score, age and body mass index (BMI). We reported a relatively high percent of depression in IBD patients, although no significant relationship was seen. Copyright © 2012 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.

Assessment of leg muscle activity using toe tapping in patients with Parkinson's disease: comparison of two types of toe tapping.

PubMed

Taniguchi, Seira; Peper, Ferdinand; Shimokawa, Tetsuya

2018-05-01

[Purpose] This study investigates two types of toe tapping, i.e., "closed," with both feet on the floor, and "open," in which the foot does not touch the ground, and evaluates their usefulness in combination with monitoring of muscle activity during toe tapping. [Subjects and Methods] The study enrolled 11 patients with Parkinson's disease (PD) and 9 controls (Controls). The tibialis anterior (TA) and gastrocnemius (GS) muscle activity during toe tapping was measured using surface electromyography. [Results] In closed tapping, the minima in GS activation with the first tap was significantly higher in patients with PD than in Controls. In open tapping, the coefficient of variation (CV) of local maxima in TA activation was significantly higher in patients with PD than in Controls. In both types of tapping, the CV of extrema in GS activities increased with disease duration, but this may be due to the long-term administration of Levodopa, which itself tends to cause excessive GS activities. [Conclusion] Closed tapping is suitable for the assessment of GS activity and can detect excessive activities, which is observed as visible movement. Open tapping, on the other hand, is suitable for assessment of TA activity.

The relationship between organised physical recreation and mental health.

PubMed

Street, Gillian; James, Ray; Cutt, Hayley

2007-12-01

The mental health benefit of participation in organised physical recreation is investigated as strategies aimed at enhancing mental health and well-being in the community have the potential to decrease social and economic costs. A literature review was undertaken to explore evidence relating to the mental health benefits of participation in organised physical recreation. Regular physical activity is widely recognised as protective against the overall burden of disease. Evaluations by government departments in Australia and the United States (US) found that people who participate in sports clubs and organised recreational activity enjoy better mental health, are more alert, and more resilient against the stresses of modern living. Participation in recreational groups and socially supported physical activity is shown to reduce stress, anxiety and depression, and reduce symptoms of Alzheimer's disease, yet more than one-third of adult Australians report no participation in sports and physical recreation. Evaluations of some programs found that physical activity is increased when the social environment is supportive and that the mental and physical benefits of participating in organised recreational activity can be experienced by people other than those directly involved with the sport or activity. This review supports the development and maintenance of organised sport and recreational activities that are socially and culturally appropriate. An increase in valid and reliable evaluations of sport and physical recreation programs would contribute to the international body of evidence of the mental health benefits of organised physical recreation.

Why Does Placement of Persons with Alzheimer's Disease into Long-term Care Improve Caregivers’ Well-Being? Examination of Psychological Mediators

PubMed Central

Mausbach, Brent T.; Chattillion, Elizabeth A.; Ho, Jennifer; Flynn, Laura M.; Tiznado, Denisse; von Känel, Roland; Patterson, Thomas L.; Grant, Igor

2014-01-01

Caregiving for individuals with Alzheimer's Disease (AD) is associated with chronic stress and elevated symptoms of depression. Placement of the care receiver (CR) into a long-term care setting may be associated with improved caregiver well-being; however, the psychological mechanisms underlying this relationship are unclear. This study evaluated whether decreases in activity restriction and increases in personal mastery mediated placement-related reductions in caregiver depressive symptoms. In a five-year longitudinal study of 126 spousal AD caregivers, we used multilevels models to evaluate placement-related changes in depressive symptoms (CESD-10), activity restriction (Activity Restriction Scale), and personal mastery (Pearlin Mastery Scale) in 44 caregivers who placed their spouses into long-term care relative to caregivers who never placed their CRs. The Monte Carlo Method for Assessing Mediation (MCMAM) was used to evaluate the significance of the indirect effect of activity restriction and personal mastery on post-placement changes in depressive symptoms. Placement of the CR was associated with significant reductions in depressive symptoms and activity restriction, while also being associated with increased personal mastery. Lower activity restriction and higher personal mastery were associated with reduced depressive symptoms. Furthermore, both variables significantly mediated the effect of placement on depressive symptoms. Placement-related reductions in activity restriction and increases in personal mastery are important psychological factors that help explain post-placement reductions in depressive symptoms. The implications for clinical care provided to caregivers are discussed. PMID:25133414

Evaluation of plasma, erythrocytes, and bronchoalveolar lavage fluid antioxidant defense system in sulfur mustard-injured patients.

PubMed

Jafari, Mahvash; Ghanei, Mostafa

2010-03-01

Sulfur mustard (SM) is a strong alkylating agent that causes acute and chronic effects on different organs following exposure. Main late respiratory complications are chronic obstructive pulmonary disease, bronchiectasis, asthma, and bronchiolitis obliterans. It seems that oxidative stress plays a major role in pathogenesis of diseases. This study was undertaken to evaluate the long-term effect of SM on plasma, erythrocytes, and brochoalveolar lavage fluid antioxidant defense system in SM-injured patients. Brochoalveolar lavage fluid, plasma, and erythrocyte samples were taken from 54 patients in the case group exposed to SM and 25 controls with chronic respiratory disease without a history of exposure to SM. Superoxide dismutase, catalase, and glutathione peroxidase activities in lavage fluid, plasma, and erythrocytes were significantly higher in case group. The increased glutathione S-transferase activity in lavage fluid was associated with a depletion of glutathione and an increase of malondialdehyde levels. There was no significant change observed in glutathione reductase activity. The data suggest that oxidative damage might have an important role for patients exposed to SM. SM may induce an oxidative stress response by depleting the antioxidant defense systems and increasing lipid peroxidation in lung cells.

Traditional chinese medicine improves activities of daily living in Parkinson's disease.

PubMed

Pan, Weidong; Kwak, Shin; Liu, Yun; Sun, Yan; Fang, Zhenglong; Qin, Baofeng; Yamamoto, Yoshiharu

2011-01-01

We evaluated the effects of a traditional Chinese medicine (TCM), named Zeng-xiao An-shen Zhi-chan 2 (ZAZ2), on patients with Parkinson's disease (PD). Among 115 patients with idiopathic PD enrolled (mean age, 64.7 ± 10.2 years old), 110 patients (M = 65, F = 45; mean age, 64.9 ± 10.7 years old) completed the study. Patients took either ZAZ2 (n = 59) or placebo granule (n = 56) in a blind manner for 13 weeks while maintaining other anti-Parkinson medications unchanged. All participants wore a motion logger, and we analyzed the power-law temporal autocorrelation of the motion logger records taken on 3 occasions (before, one week, and 13 weeks after the drug administration). Drug efficacy was evaluated with the conventional Unified Parkinson Disease Rating Scale (UPDRS), as well as the power-law exponent α, which corresponds to the level of physical activity of the patients. ZAZ2 but not placebo granule improved the awake-sleep rhythm, the UPDRS Part II, Part II + III, and Part IV scores, and the α values. The results indicate that ZAZ2 improved activities of daily living (ADL) of parkinsonism and, thus, is a potentially suitable drug for long-term use.

Design, synthesis and biological evaluation of 4'-aminochalcone-rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer's disease.

PubMed

Xiao, Ganyuan; Li, Yan; Qiang, Xiaoming; Xu, Rui; Zheng, Yunxiaozhu; Cao, Zhongcheng; Luo, Li; Yang, Xia; Sang, Zhipei; Su, Fu; Deng, Yong

2017-02-01

A series of 4'-aminochalcone-revastigmine hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. The results showed that most of these compounds exhibited good multifunctional activities. In particular, compound 6c displayed the best inhibitory potency on acetylcholinesterase (IC 50 =4.91μM), and significant antioxidative activity with a value 2.83-fold of Trolox. The kinetic analysis of AChE inhibition revealed that 6c showed mixed-type inhibition, binding simultaneously to the catalytic active site and peripheral anionic site of AChE. In addition, 6c inhibited self-induced Aβ 1-42 aggregation and Cu 2+ -induced Aβ 1-42 aggregation by 89.5% and 79.7% at 25μM respectively, as well as acted as a selective monoamine oxidase B inhibitor (IC 50 =0.29μM) and a selective biometal chelator. Furthermore, 6c could cross the blood-brain barrier in vitro. Based on these results, Compound 6c could be considered as a very promising lead compound for Alzheimer's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relation of Perceived Health Competence to Physical Activity in Patients With Coronary Heart Disease.

PubMed

Bachmann, Justin M; Mayberry, Lindsay S; Wallston, Kenneth A; Huang, Shi; Roumie, Christianne L; Muñoz, Daniel; Patel, Niral J; Kripalani, Sunil

2018-05-01

Physical inactivity is highly associated with mortality, especially in patients with coronary heart disease. We evaluated the effect of perceived health competence, a patient's belief in his or her ability to achieve health-related goals, on cumulative physical activity levels in the Mid-South Coronary Heart Disease Cohort Study. The Mid-South Coronary Heart Disease Cohort Study consists of 2,587 outpatients (32% were female) with coronary heart disease at an academic medical center network in the United States. Cumulative physical activity was quantified in metabolic equivalent (MET)-minutes per week with the International Physical Activity Questionnaire. We investigated associations between the 2-item Perceived Health Competence Scale (PHCS-2) and MET-minutes/week after adjusting for co-morbidities and psychosocial factors with linear regression. Nearly half of participants (47%) exhibited low physical activity levels (<600 MET-minutes/week). Perceived health competence was highly associated with physical activity after multivariable adjustment. A nonlinear relation was observed, with the strongest effect on physical activity occurring at lower levels of perceived health competence. There was effect modification by gender (p = 0.03 for interaction). The relation between perceived health competence and physical activity was stronger in women compared with men; an increase in the PHCS-2 from 3 to 4 was associated with a 73% increase in MET-minutes/week in women (95% confidence interval 43% to 109%, p <0.0001) compared with a 53% increase in men (95% confidence interval 27% to 84%, p <0.0001). In conclusion, low perceived health competence was strongly associated with less physical activity in patients with coronary heart disease and may represent a potential target for behavioral interventions. Published by Elsevier Inc.

Detection of inflammatory bowel disease in adults and children: evaluation of a new isotopic technique.

PubMed Central

Dawson, D J; Khan, A N; Miller, V; Ratcliffe, J F; Shreeve, D R

1985-01-01

The distribution of radioactivity after the oral administration of sucralfate labelled with technetium-99m was studied in 33 patients with Crohn's disease (13 adults, 20 children), 10 with ulcerative colitis (four adults), and 29 controls (23 with upper intestinal disease, four irritable bowel, one hypolactasia, and one malrotation of the gut). Positive scans were obtained in all patients with ulcerative colitis and 29 of 31 with active Crohn's disease. The scans of two patients with inactive Crohn's disease were negative. There were two false negative scans in patients with Crohn's colitis and one false positive scan. Overall, sensitivity was 95% and specificity 97%. Comparison with radiology in 39 patients showed similar distribution of disease in 24 and more extensive disease in 12. The scan was inexpensive, simple to perform, well tolerated, allowed small and large bowel to be visualised simultaneously, and used a lower dose of radiation than barium studies. It may prove useful as a screening test for inflammatory bowel disease and in the serial assessment of disease activity. Images FIG 1 FIG 2 FIG 3 FIG 4 PMID:3933613

Behçet syndrome manifestations and activity in the United States versus Turkey -- a cross-sectional cohort comparison.

PubMed

Sibley, Cailin; Yazici, Yusuf; Tascilar, Koray; Khan, Nafiz; Bata, Yasmin; Yazici, Hasan; Goldbach-Mansky, Raphaela; Hatemi, Gulen

2014-07-01

To compare clinical manifestations and activity of Behçet syndrome (BS) in the United States versus Turkey using validated outcome measures. Consecutive patients with BS from the US National Institutes of Health (NIH), New York University, and the University of Istanbul were evaluated. Disease activity was measured using the Behçet's Syndrome Activity Scale (BSAS) and the Behçet's Disease Current Activity Form (BDCAF) with quality of life measured by the Behçet Disease Quality of Life (BDQOL) form. One-way ANOVA, t-tests, and multivariate regression analyses were performed. Mean age did not differ between sites; however, more women were seen in the United States versus in Turkey (p < 0.001), and disease duration was longer in the United States (p = 0.02). Organ manifestations were similar for oral and genital ulcers, skin disease, arthralgia, eye disease, and thrombosis. However, more gastrointestinal (p < 0.001) and neurologic disease (p = 0.003) was seen in the United States. BSAS and BDCAF scores were worse in the United States compared to Turkey (p = 0.013 and < 0.001, respectively). Worse mean BDQOL scores were observed at the NIH compared to Istanbul (not significant). Multivariable regression models showed worse scores in ethnically atypical patients for BSAS and BDCAF (p = 0.04 and p = 0.001), American patients for BDCAF (p = 0.01), older age for BDCAF (p = 0.005), and women for BDQOL (p = 0.01). Demographic and clinical manifestations of BS differ between sites with higher disease activity in the United States compared to Turkey. Referral patterns, age, sex, ethnicity, and country of origin may be important in these differences. These observations raise the question of whether pathogenic mechanisms differ in Turkish and American patients.

Antitrypanosomal, antileishmanial and cytotoxic activities of Brazilian red propolis and plant resin of Dalbergia ecastaphyllum (L) Taub.

PubMed

Regueira-Neto, Marcos da Silveira; Tintino, Saulo Relison; Rolón, Miriam; Coronal, Cathia; Vega, Maria C; de Queiroz Balbino, Valdir; de Melo Coutinho, Henrique Douglas

2018-04-14

The treatment for leishmaniasis and Chagas disease can be hard and painful, such that many patients give up on the treatment. In order to find an alternative path for the treatment of these diseases, researchers are using natural products to fight these parasites. The aim of this study was to evaluate the antiprotozoan and cytotoxic activities of red propolis samples collected from different Brazilian states and seasons whilst searching for possible activity differences. We also compared the red propolis results with the ones obtained for the plant resin extract collected from Dalbergia ecastaphyllum trees. The hydroethanolic red propolis extracts from Pernambuco and Alagoas, and the D. ecastaphyllum resin were evaluated regarding their antileishmanial, antitrypanosomal and cytotoxic activity. All extracts showed antiprotozoan and cytotoxic activity. RP-PER showed to be more cytotoxic against protozoan parasites and fibroblast cells. All propolis extracts showed a higher cytotoxic activity when compared to resin extracts. The propolis sample collected in Pernambuco during the rainy season killed the parasites with lower concentrations than the sample collected in the dry season. The IC 50 observed against the parasites could be used without high fibroblast cell damage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Antifungal and antioxidant activities of mature leaves of Myrcia splendens (Sw.) DC.

PubMed

Pontes, F C; Abdalla, V C P; Imatomi, M; Fuentes, L F G; Gualtieri, S C J

2018-05-07

In recent years, natural products with antifungal and antioxidant activities are being increasingly researched for a more sustainable alternative to the chemicals currently used for the same purpose. The plant pathogenic fungus Alternaria alternata is a causative agent of diseases in citrus, leading to huge economic losses. Antioxidants are important for the production of medicines for various diseases that may be related to the presence of free radicals, such as cancer, and in the cosmetic industry as an anti-aging agent and the food industry as preservatives. This study evaluated the antifungal and antioxidant potential of extracts of mature leaves of Myrcia splendens, a tree species that occurs in the Brazilian Cerrado. The antioxidant potential was analyzed by an assay of 1,1-diphenyl-2-picrylhydrazyl radical-scavenging method, and the antifungal activity was assessed through the evaluation of mycelial growth. Majority of the extracts exhibited a strong antioxidant activity, especially the acetonic extract (4A). The antioxidant activity may be related to the presence of phenolic compounds. However, the extracts showed no inhibitory activity of mycelial growth of the fungus tested, with the exception of dichloromethanic extract (2B), which had an inhibitory effect (10.2%) at the end of testing.

A Scientometric Evaluation of the Chagas Disease Implementation Research Programme of the PAHO and TDR

PubMed Central

Carbajal-de-la-Fuente, Ana Laura; Yadón, Zaida E.

2013-01-01

The Special Programme for Research and Training in Tropical Diseases (TDR) is an independent global programme of scientific collaboration cosponsored by the United Nations Children's Fund, the United Nations Development Program, the World Bank, and the World Health Organization. TDR's strategy is based on stewardship for research on infectious diseases of poverty, empowerment of endemic countries, research on neglected priority needs, and the promotion of scientific collaboration influencing global efforts to combat major tropical diseases. In 2001, in view of the achievements obtained in the reduction of transmission of Chagas disease through the Southern Cone Initiative and the improvement in Chagas disease control activities in some countries of the Andean and the Central American Initiatives, TDR transferred the Chagas Disease Implementation Research Programme (CIRP) to the Communicable Diseases Unit of the Pan American Health Organization (CD/PAHO). This paper presents a scientometric evaluation of the 73 projects from 18 Latin American and European countries that were granted by CIRP/PAHO/TDR between 1997 and 2007. We analyzed all final reports of the funded projects and scientific publications, technical reports, and human resource training activities derived from them. Results about the number of projects funded, countries and institutions involved, gender analysis, number of published papers in indexed scientific journals, main topics funded, patents inscribed, and triatomine species studied are presented and discussed. The results indicate that CIRP/PAHO/TDR initiative has contributed significantly, over the 1997–2007 period, to Chagas disease knowledge as well as to the individual and institutional-building capacity. PMID:24244761

Evaluation of the association between Hispanic ethnicity and disease activity and severity in a large cohort of patients with juvenile idiopathic arthritis.

PubMed

Pelajo, Christina F; Angeles-Han, Sheila T; Prahalad, Sampath; Sgarlat, Caitlin M; Davis, Trevor E; Miller, Laurie C; Lopez-Benitez, Jorge M

2013-10-01

To examine the association between ethnicity and disease activity in patients with juvenile idiopathic arthritis (JIA), and to determine the association of ethnicity with disease severity and disability in this population. CARRAnet, a US database containing information (collected between May 2010 and June 2011) on almost 3,000 subjects with JIA, was used. Demographic variables were compared between Hispanic patients and non-Hispanic patients. Mann-Whitney and chi-square tests were used to compare indicators of disease activity, as well as imaging evidence of joint damage, and Childhood Health Assessment Questionnaire (CHAQ) scores between ethnicities. Two linear regression models were used to determine the association of ethnicity with number of active joints in JIA, and the association between ethnicity and disability (CHAQ scores). A total of 2,704 patients with JIA (277 Hispanic; 2,427 non-Hispanic) were included. Income and health insurance coverage were higher in non-Hispanics. RF-positive polyarticular JIA, positive RF and anti-CCP, as well as use of systemic steroids were more frequent in Hispanics. Imaging evidence of joint damage was present in 32 % of the Hispanic patients compared to 24 % of the non-Hispanic patients (p = 0.008). In multivariate linear regression analyses, the number of active joints was significantly higher in Hispanics than in non-Hispanics (p = 0.03), as well as CHAQ scores (p = 0.003), after adjusting for confounders. Hispanic patients with JIA had higher disease activity than non-Hispanic patients, as well as higher disease severity and disability. Since ethnicity influences disease activity, severity, and disability, different management and treatment plans should be planned accordingly.

Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn's disease.

PubMed

Sands, B E; Bank, S; Sninsky, C A; Robinson, M; Katz, S; Singleton, J W; Miner, P B; Safdi, M A; Galandiuk, S; Hanauer, S B; Varilek, G W; Buchman, A L; Rodgers, V D; Salzberg, B; Cai, B; Loewy, J; DeBruin, M F; Rogge, H; Shapiro, M; Schwertschlag, U S

1999-07-01

Recombinant human interleukin 11 (rhIL-11) is a cytokine with thrombocytopoietic activity and anti-inflammatory and mucosal protective effects. The objectives of this study were to investigate the safety and tolerability of rhIL-11 in patients with Crohn's disease and to explore the effects of dose and schedule on platelet count and Crohn's disease activity. A multicenter, double-masked, placebo-controlled, dose-escalation study of 76 patients with active Crohn's disease was performed. Patients were randomized to receive subcutaneous placebo or rhIL-11 at doses of 5, 16, or 40 microgram. kg-1. wk-1 given 2 or 5 times weekly for 3 weeks. Clinical and laboratory safety data were recorded, and disease activity was measured at each visit. Subcutaneous injection of rhIL-11 generally was well tolerated. Significantly greater increases in platelet counts were found among patients receiving rhIL-11 40 microgram. kg-1. wk-1 as 2 or 5 weekly doses and 16 microgram. kg-1. week-1 as 5 weekly doses compared with patients receiving placebo (P < 0.05). Patients receiving 16 microgram. kg-1. wk-1 had the highest clinical response rates, with a response seen in 42% of patients (5/12) receiving 5 weekly doses and 33% of patients (4/12) receiving 2 weekly doses, compared with 7% of patients (1/15) receiving placebo. Short-term treatment with rhIL-11 is well tolerated in patients with active Crohn's disease. The thrombocytopoietic effect of rhIL-11 seems to be both dose and schedule dependent and may be minimized with retained clinical benefit in Crohn's disease at 16 microgram. kg-1. wk-1 given in 2 equal doses.

Cross-cultural adaptation and validation of the Behcet's Disease Current Activity Form in Korea.

PubMed

Choi, Hyo Jin; Seo, Mi Ryoung; Ryu, Hee Jung; Baek, Han Joo

2015-09-01

This study was undertaken to perform a cross-cultural adaptation of the Behcet's Disease Current Activity Form (BDCAF, version 2006) questionnaire to the Korean language and to evaluate its reliability and validity in a population of Korean patients with Behcet's disease (BD). A cross-cultural study was conducted among patients with BD who attended our rheumatology clinic between November 2012 and March 2013. There were 11 males and 35 females in the group. The mean age of the participants was 48.5 years and the mean disease duration was 6.4 years. The first BDCAF questionnaire was completed on arrival and the second assessment was performed 20 minutes later by a different physician. The test-retest reliability was analyzed by computing κ statistics. Kappa scores of > 0.6 indicated a good agreement. To assess the validity, we compared the total BDCAF score with the patient's/clinician's perception of disease activity and the Korean version of the Behcet's Disease Quality of Life (BDQOL). For the test-retest reliability, good agreements were achieved on items such as headache, oral/genital ulceration, erythema, skin pustules, arthralgia, nausea/vomiting/abdominal pain, and diarrhea with altered/frank blood per rectum. Moderate agreement was observed for eye and nervous system involvement. We achieved a fair agreement for arthritis and major vessel involvement. Significant correlations were obtained between the total BDCAF score with the BDQOL and the patient's/clinician's perception of disease activity p < 0.05). The Korean version of the BDCAF is a reliable and valid instrument for measuring current disease activity in Korean BD patients.

[The usefulness of portable 24-hour polygraphic monitoring--evaluation of autonomic nervous activity of the patients with ischemic heart disease by using heart rate variability during sleep].

PubMed

Adachi, M

1995-02-01

Portable 24-hour polygraphic monitorings were performed on 109 cases with neurological or cardiovascular disorders, sleep disturbances and metabolic diseases to clarify its usefulness and limitations. Moreover, an evaluation of autonomic nervous activity was done in different stages of sleep in normal young (n = 9), normal middle-aged subjects (n = 8) and patients with ischemic heart disease (n = 7) using power spectral analysis of heart rate. The parameters recorded in this study were electroencepharogram(EEG), electrooculogram, electromyogram of chin muscles, electrocardiogram, respiratory curve, walking pulse and body position. Using polygraphic monitoring, the patients with cardiac arrhythmia showed abnormal EEG in 20% and those with neurological events in 86.7%. The improvement of sleep structure was found after pacemaker implantation in the patients with bradyarrhythmias (75%). Time spans of slow wave sleep and REM sleep of patients with ischemic heart disease decreased significantly from 120.9 +/- 40.6 min to 79.1 +/- 25.3 min, 112.8 +/- 16.5 min to 63.6 +/- 23.6 min, respectively (p < 0.05). RR50, that is number of R -R intervals greater than 50msec compared to the preceding R-R interval, decreased significantly in each stage of sleep in the patients with ischemic heart disease compared to normal subjects (stage 2: 18.3 +/- 6.1/min to 3.8 +/- 3.0/min, p < 0.01; SWS: 7.8 +/- 8.0/min to 3.2 +/- 2.5/min, p < 0.05; REM: 17.9 +/- 6.0/min to 4.4 +/- 4.3/min, p < 0.01). The HF power in all stages of sleep showed a trend of the decrease in the patients with ischemic heart disease. In REM sleep, the LF power in patients with ischemic disease was lower significantly compared to that in normal middle-aged subjects (6.1 +/- 3.2 to 12.1 +/- 4.1, p < 0.05). The L/H ratio also decreased significantly (1.08 +/- 0.30 vs. 2.35 +/- 1.03, p < 0.05). The slope of 1/fx above 0.15Hz in IHD patients was less in stage 2 (-0.404 +/- 0.280 vs. -0.849 +/- 0.183, p < 0.01) and in REM sleep (-0.294 +/- 0.368 vs. -0.665 +/- 0.291, p < 0.05). Above results suggest the involvement of a decrease of sympathetic activity in addition to decrease of parasympathetic activity especially in REM sleep in the patients with ischemic heart disease. In conclusion, polygraphic monitoring is useful for a detection of abnormality of EEG and an evaluation of autonomic activity in cardiovascular disorders.

Quality of life in inflammatory bowel disease patients: A cross-sectional study.

PubMed

Habibi, Farzaneh; Habibi, Mohammad Emadoddin; Gharavinia, Ali; Mahdavi, Sadegh Baradaran; Akbarpour, Mohammad Javad; Baghaei, Abdolmehdi; Emami, Mohammad Hassan

2017-01-01

Inflammatory bowel disease (IBD) has a significant impact on health-related quality of life (HRQOL). This study aims to investigate the variables which can be attributed to HRQOL in IBD patients. Seventy-one patients filled in IBD questionnaire (IBDQ-32), Pittsburgh sleep quality index questionnaire, and sociodemographic questionnaire. Disease activity was assessed by Crohn's disease activity index (CDAI) and ulcerative colitis activity index (UCAI). The correlations of sleep quality, sociodemographic variables, and disease characteristics with IBDQ were investigated. IBDQ-32 mean score was lower in patients who had hospitalization ( P = 0.01), poor sleep quality ( P < 0.001), anemia ( P = 0.03), more severe disease ( P = 0.01), and those who had not consumed folic acid ( P = 0.01) relative to their counterparts. A multivariate regression analysis identified the predictors of decreased HRQOL as not consuming folic acid ( P = 0.008), poor sleep quality ( P = 0.014), and disease severity ( P = 0.043). Impaired HRQOL was significantly associated with poor sleep quality, lack of folic acid consumption, and disease severity in IBD patients. Therefore, evaluation of folic acid level and efficacy of its supplementation in prospective studies is recommended. Treatment of sleep disturbance with pharmacological agents and nonpharmacological methods should be kept in mind as well.

Leprosy: ancient disease remains a public health problem nowadays.

PubMed

Noriega, Leandro Fonseca; Chiacchio, Nilton Di; Noriega, Angélica Fonseca; Pereira, Gilmayara Alves Abreu Maciel; Vieira, Marina Lino

2016-01-01

Despite being an ancient disease, leprosy remains a public health problem in several countries -particularly in India, Brazil and Indonesia. The current operational guidelines emphasize the evaluation of disability from the time of diagnosis and stipulate as fundamental principles for disease control: early detection and proper treatment. Continued efforts are needed to establish and improve quality leprosy services. A qualified primary care network that is integrated into specialized service and the development of educational activities are part of the arsenal in the fight against the disease, considered neglected and stigmatizing.

Light and sound - emerging imaging techniques for inflammatory bowel disease

PubMed Central

Knieling, Ferdinand; Waldner, Maximilian J

2016-01-01

Patients with inflammatory bowel disease are known to have a high demand of recurrent evaluation for therapy and disease activity. Further, the risk of developing cancer during the disease progression is increasing from year to year. New, mostly non-radiant, quick to perform and quantitative methods are challenging, conventional endoscopy with biopsy as gold standard. Especially, new physical imaging approaches utilizing light and sound waves have facilitated the development of advanced functional and molecular modalities. Besides these advantages they hold the promise to predict personalized therapeutic responses and to spare frequent invasive procedures. Within this article we highlight their potential for initial diagnosis, assessment of disease activity and surveillance of cancer development in established techniques and recent advances such as wide-view full-spectrum endoscopy, chromoendoscopy, autofluorescence endoscopy, endocytoscopy, confocal laser endoscopy, multiphoton endoscopy, molecular imaging endoscopy, B-mode and Doppler ultrasound, contrast-enhanced ultrasound, ultrasound molecular imaging, and elastography. PMID:27433080

Analysis of correlations between selected endothelial cell activation markers, disease activity, and nailfold capillaroscopy microvascular changes in systemic lupus erythematosus patients.

PubMed

Ciołkiewicz, Mariusz; Kuryliszyn-Moskal, Anna; Klimiuk, Piotr Adrian

2010-02-01

The aim of the study was to evaluate the correlation between selected serum endothelial cell activation markers such as vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble thrombomodulin (sTM), soluble E-selectin (sE-selectin), disease activity, and microvascular changes determined by nailfold capillaroscopy in patients with systemic lupus erythematosus (SLE). Serum levels of VEGF, ET-1, sTM, and sE-selectin were determined by an enzyme-linked immunosorbent assay in 80 SLE patients. The disease activity was measured with Systemic Lupus Erythematosus Disease Activity Index score. Nailfold capillaroscopy was performed in all patients. Positive correlation was found between VEGF and both ET-1 (r = 0.294, p < 0.01) and sE-selectin (r = 0.274, p < 0.05) serum levels as well as between sTM and ET-1 (r = 0.273, p < 0.05) serum concentrations. We noticed also positive correlation between VEGF (r = 0.224, p < 0.05) and ET-1 (r = 0.471, p < 0.001) serum levels and disease activity, and also between VEGF serum concentration and grade of morphological changes observed by nailfold capillaroscopy (r = 0.458, p < 0.001). There was also positive correlation between capillaroscopic score and disease activity (r = 0.339, p < 0.01). Our data suggest that correlation between VEGF and both ET-1 and E-selectin serum levels as well as between sTM and ET-1 serum concentrations may reflect their participation in the pathogenesis of SLE. VEGF seems to reflect changes in microcirculation in the course of SLE, visualised by nailfold capillaroscopy. The relationship between changes in nailfold capillaroscopy, endothelial cell activation markers, and the clinical activity of SLE points to an important role of microvascular abnormalities in the clinical manifestation of the disease.

Ocular Blood Flow Changes in Behçet Disease Patients with/without Thrombotic Disease

PubMed Central

Yüksel, Harun; Türkcü, Fatih M.; Hamidi, Cihat; Cingü, Abdullah K.; Çinar, Yasin; Şahin, Muhammed; Özkurt, Zeynep; Çaça, İhsan

2014-01-01

ABSTRACT In this study, the authors aimed to evaluate ocular blood flow changes in Behçet disease (BD) with and without thrombotic disease. Ninety eyes of 90 patients with a diagnosis of BD (30 eyes with active uveitis, 23 eyes with inactive uveitis, 25 eyes without ocular involvement, and 12 eyes without ocular involvement and with a history of thrombosis) and 30 eyes of 30 age- and sex-matched control patients without any systemic disease with a total of 120 eyes were evaluated. In all cases, ophthalmic, central retinal, and ciliary artery flow parameters were measured with colour Doppler ultrasonography (CDU). The ocular blood flow parameters of all vessels in patients with active uveitis were found to be affected. All the flow parameters in the CRAs of the study groups were significantly different from the control group (p < 0.001). Additionally, in non-ocular BD patients with thrombosis, blood flow parameters were affected more than the parameters in non-ocular BD patients without thrombosis and control patients. In conclusion, major haemodynamic changes were observed using CDU in the ophthalmic vessels of ocular Behçet patients. Also, CDU may detect ocular blood flow alterations before initial ocular clinical manifestations appear in BD patients PMID:27928286

Ocular Blood Flow Changes in Behçet Disease Patients with/without Thrombotic Disease.

PubMed

Yüksel, Harun; Türkcü, Fatih M; Hamidi, Cihat; Cingü, Abdullah K; Çinar, Yasin; Şahin, Muhammed; Özkurt, Zeynep; Çaça, İhsan

2014-01-01

In this study, the authors aimed to evaluate ocular blood flow changes in Behçet disease (BD) with and without thrombotic disease. Ninety eyes of 90 patients with a diagnosis of BD (30 eyes with active uveitis, 23 eyes with inactive uveitis, 25 eyes without ocular involvement, and 12 eyes without ocular involvement and with a history of thrombosis) and 30 eyes of 30 age- and sex-matched control patients without any systemic disease with a total of 120 eyes were evaluated. In all cases, ophthalmic, central retinal, and ciliary artery flow parameters were measured with colour Doppler ultrasonography (CDU). The ocular blood flow parameters of all vessels in patients with active uveitis were found to be affected. All the flow parameters in the CRAs of the study groups were significantly different from the control group ( p  < 0.001). Additionally, in non-ocular BD patients with thrombosis, blood flow parameters were affected more than the parameters in non-ocular BD patients without thrombosis and control patients. In conclusion, major haemodynamic changes were observed using CDU in the ophthalmic vessels of ocular Behçet patients. Also, CDU may detect ocular blood flow alterations before initial ocular clinical manifestations appear in BD patients.

Changes in functional health status of older women with heart disease: evaluation of a program based on self-regulation.

PubMed

Clark, N M; Janz, N K; Dodge, J A; Schork, M A; Fingerlin, T E; Wheeler, J R; Liang, J; Keteyian, S J; Santinga, J T

2000-03-01

This study involving 570 women aged 60 years or older with heart disease, assessed the effects of a disease management program on physical functioning, symptom experience, and psychosocial status. Women were randomly assigned to control or program groups. Six to eight women met weekly with a health educator and peer leader over 4 weeks to learn self-regulation skills with physical activity as the focus. Evaluative data were collected through telephone interviews, physical assessments, and medical records at baseline and 4 and 12 months post baseline. At 12 months, compared with controls, program women were less symptomatic (p < .01), scored better on the physical dimension of the Sickness Impact Profile (SIP; p < 0.05), had improved ambulation as measured by the 6-minute walk (p < 0.01), and lost more body weight (p < .001). No differences related to psychosocial factors as measured by the SIP were noted. A self-regulation-based program that was provided to older women with heart disease and that focused on physical activity and disease management problems salient to them, improved their physical functioning and symptom experience. Psychosocial benefit was not evident and may be a result of measurement error or due to insufficient program time spent on psychosocial aspects of functioning.

ADVANTAGES OF REMOTE MONITORING THE ACTIVITY OF PATIENTS WITH AXIAL SPONDYLITIS (PROGRESS STUDY).

PubMed

Gaidukova, I Z; Akulova, A I; Aparkina, A V; Rebrov, A P

To improve the quality of treatment of patients with spondyloarthrities based on analysis of adherence to therapy and its timely correction by regular remote monitoring the activity of the disease. 46 patents with axial spondylitis (ankylosing spondylitis, non-radiographic spondylitis) were interviewed by phone once in 4 weeks for 18 months with a 3 month interval after 12 months. 96 patients underwent routine outpatient examination for the evaluation of the main parameters of the disease. Arbitrarily examined patients with spondyloarthritis reported poor compliance with therapy and its low efficiency. During 18 months, 79% of the patients were recommended treatment with TNF-a inhibitors. Only 18.5% of them in the remote monitoring group failed to reach the BASDAI index S 4 whereas 73.9% of the patients examined remotely for 1 year had low activity of the disease or its partial remission. An increased period between two phone interviews from 1 to 3 months in 58.6% patients with low activity of the disease was associated with impaired adherence to therapy (decreased intake of the anti-inflammatory drug or its withdrawal) that did not lead to enhancement of activity during 3 months after the change in the treatment. Remote monitoring of activity of the disease (one phone interview every 4 weeks) allows to decrease it or reach remission in 73.9% of the patients with axial spondyloarthritis. The decrease in the frequency of telephone calls to one every 3 months results in the impairment of compliance with therapy but does not lead to increase of disease activity in the short run.

Relative value of the lumbar spine and hip bone mineral density and bone turnover markers in men with ankylosing spondylitis.

PubMed

Muntean, Laura; Rojas-Vargas, Marena; Font, Pilar; Simon, Siao-Pin; Rednic, Simona; Schiotis, Ruxandra; Stefan, Simona; Tamas, Maria M; Bolosiu, Horatiu D; Collantes-Estévez, Eduardo

2011-05-01

The purpose of this study is to evaluate bone mineral density (BMD) and bone turnover markers in men with ankylosing spondylitis (AS) and to determine their relationship with clinical features and disease activity. Serum carboxi terminal cross-linked telopeptide of type I collagen (CTX), osteocalcin (OC) levels, and BMD of lumbar spine and proximal femur were evaluated in 44 males with AS, 18-60 years of age, and compared with those of 39 age-matched healthy men. Men with AS had a significantly lower BMD at the femoral neck and total hip as compared to age-matched controls (all p < 0.01). Osteopaenia or osteoporosis was found in 59.5% AS patients at the lumbar spine and in 47.7% at the femoral neck. Mean serum levels of OC and CTX were similar in AS patients and controls. There were no significant differences in BMD and bone turnover markers when comparing subgroups stratified according to disease duration or presence of peripheral arthritis. No correlations were found between disease activity markers and BMD or OC and CTX. In a cohort of relatively young males with AS, we found a high incidence of osteopaenia and osteoporosis. Disease activity and duration did not show any significant influence on BMD or serum levels of OC and CTX.

Comparison of quantitative cytomegalovirus (CMV) PCR in plasma and CMV antigenemia assay: clinical utility of the prototype AMPLICOR CMV MONITOR test in transplant recipients.

PubMed

Caliendo, A M; St George, K; Kao, S Y; Allega, J; Tan, B H; LaFontaine, R; Bui, L; Rinaldo, C R

2000-06-01

The correlation between the prototype AMPLICOR CMV MONITOR test (Roche Molecular Systems), a quantitative PCR assay, and the cytomegalovirus (CMV) pp65 antigenemia assay was evaluated in transplant recipients. Sequential blood specimens were collected on 29 patients (491 specimens), the leukocyte fraction was tested by CMV antigenemia, and quantitative PCR was performed on plasma specimens. None of the 15 patients (242 specimens) who were antigenemia negative were positive for CMV DNA by PCR, and none of these patients developed active CMV disease. There were 14 antigenemia-positive patients, 8 of whom developed active CMV disease. In all patients, there was a good association between the antigenemia and PCR assays. Ganciclovir-resistant virus was isolated from three patients with active CMV disease. These three patients had persistently elevated levels of antigenemia and CMV DNA by PCR when resistance to ganciclovir developed. This standardized, quantitative CMV PCR assay on plasma has clinical utility for the diagnosis of active disease and in monitoring the response to antiviral therapy in transplant recipients.

Comparison of Quantitative Cytomegalovirus (CMV) PCR in Plasma and CMV Antigenemia Assay: Clinical Utility of the Prototype AMPLICOR CMV MONITOR Test in Transplant Recipients

PubMed Central

Caliendo, Angela M.; St. George, Kirsten; Kao, Shaw-Yi; Allega, Jessica; Tan, Ban-Hock; LaFontaine, Robert; Bui, Larry; Rinaldo, Charles R.

2000-01-01

The correlation between the prototype AMPLICOR CMV MONITOR test (Roche Molecular Systems), a quantitative PCR assay, and the cytomegalovirus (CMV) pp65 antigenemia assay was evaluated in transplant recipients. Sequential blood specimens were collected on 29 patients (491 specimens), the leukocyte fraction was tested by CMV antigenemia, and quantitative PCR was performed on plasma specimens. None of the 15 patients (242 specimens) who were antigenemia negative were positive for CMV DNA by PCR, and none of these patients developed active CMV disease. There were 14 antigenemia-positive patients, 8 of whom developed active CMV disease. In all patients, there was a good association between the antigenemia and PCR assays. Ganciclovir-resistant virus was isolated from three patients with active CMV disease. These three patients had persistently elevated levels of antigenemia and CMV DNA by PCR when resistance to ganciclovir developed. This standardized, quantitative CMV PCR assay on plasma has clinical utility for the diagnosis of active disease and in monitoring the response to antiviral therapy in transplant recipients. PMID:10834964

Ebola Virus Disease Is Characterized by Poor Activation and Reduced Levels of Circulating CD16+ Monocytes.

PubMed

Lüdtke, Anja; Ruibal, Paula; Becker-Ziaja, Beate; Rottstegge, Monika; Wozniak, David M; Cabeza-Cabrerizo, Mar; Thorenz, Anja; Weller, Romy; Kerber, Romy; Idoyaga, Juliana; Magassouba, N'Faly; Gabriel, Martin; Günther, Stephan; Oestereich, Lisa; Muñoz-Fontela, César

2016-10-15

A number of previous studies have identified antigen-presenting cells (APCs) as key targets of Ebola virus (EBOV), but the role of APCs in human Ebola virus disease (EVD) is not known. We have evaluated the phenotype and kinetics of monocytes, neutrophils, and dendritic cells (DCs) in peripheral blood of patients for whom EVD was diagnosed by the European Mobile Laboratory in Guinea. Acute EVD was characterized by reduced levels of circulating nonclassical CD16 + monocytes with a poor activation profile. In survivors, CD16 + monocytes were activated during recovery, coincident with viral clearance, suggesting an important role of this cell subset in EVD pathophysiology. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity.

PubMed

Curtis, Jeffrey R; van der Helm-van Mil, Annette H; Knevel, Rachel; Huizinga, Tom W; Haney, Douglas J; Shen, Yijing; Ramanujan, Saroja; Cavet, Guy; Centola, Michael; Hesterberg, Lyndal K; Chernoff, David; Ford, Kerri; Shadick, Nancy A; Hamburger, Max; Fleischmann, Roy; Keystone, Edward; Weinblatt, Michael E

2012-12-01

Quantitative assessment of disease activity in rheumatoid arthritis (RA) is important for patient management, and additional objective information may aid rheumatologists in clinical decision making. We validated a recently developed multibiomarker disease activity (MBDA) test relative to clinical disease activity in diverse RA cohorts. Serum samples were obtained from the Index for Rheumatoid Arthritis Measurement, Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study, and Leiden Early Arthritis Clinic cohorts. Levels of 12 biomarkers were measured and combined according to a prespecified algorithm to generate the composite MBDA score. The relationship of the MBDA score to clinical disease activity was characterized separately in seropositive and seronegative patients using Pearson's correlations and the area under the receiver operating characteristic curve (AUROC) to discriminate between patients with low and moderate/high disease activity. Associations between changes in MBDA score and clinical responses 6-12 weeks after initiation of anti-tumor necrosis factor or methotrexate treatment were evaluated by the AUROC. The MBDA score was significantly associated with the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) in both seropositive (AUROC 0.77, P < 0.001) and seronegative (AUROC 0.70, P < 0.001) patients. In subgroups based on age, sex, body mass index, and treatment, the MBDA score was associated with the DAS28-CRP (P < 0.05) in all seropositive and most seronegative subgroups. Changes in the MBDA score at 6-12 weeks could discriminate both American College of Rheumatology criteria for 50% improvement responses (P = 0.03) and DAS28-CRP improvement (P = 0.002). Changes in the MBDA score at 2 weeks were also associated with subsequent DAS28-CRP response (P = 0.02). Our findings establish the criterion and discriminant validity of a novel multibiomarker test as an objective measure of RA disease activity to aid in the management of RA in patients with this condition. Copyright © 2012 by the American College of Rheumatology.

Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity

PubMed Central

Curtis, Jeffrey R; van der Helm-van Mil, Annette H; Knevel, Rachel; Huizinga, Tom W; Haney, Douglas J; Shen, Yijing; Ramanujan, Saroja; Cavet, Guy; Centola, Michael; Hesterberg, Lyndal K; Chernoff, David; Ford, Kerri; Shadick, Nancy A; Hamburger, Max; Fleischmann, Roy; Keystone, Edward; Weinblatt, Michael E

2012-01-01

Objective Quantitative assessment of disease activity in rheumatoid arthritis (RA) is important for patient management, and additional objective information may aid rheumatologists in clinical decision making. We validated a recently developed multibiomarker disease activity (MBDA) test relative to clinical disease activity in diverse RA cohorts. Methods Serum samples were obtained from the Index for Rheumatoid Arthritis Measurement, Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study, and Leiden Early Arthritis Clinic cohorts. Levels of 12 biomarkers were measured and combined according to a prespecified algorithm to generate the composite MBDA score. The relationship of the MBDA score to clinical disease activity was characterized separately in seropositive and seronegative patients using Pearson's correlations and the area under the receiver operating characteristic curve (AUROC) to discriminate between patients with low and moderate/high disease activity. Associations between changes in MBDA score and clinical responses 6–12 weeks after initiation of anti–tumor necrosis factor or methotrexate treatment were evaluated by the AUROC. Results The MBDA score was significantly associated with the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) in both seropositive (AUROC 0.77, P < 0.001) and seronegative (AUROC 0.70, P < 0.001) patients. In subgroups based on age, sex, body mass index, and treatment, the MBDA score was associated with the DAS28-CRP (P < 0.05) in all seropositive and most seronegative subgroups. Changes in the MBDA score at 6–12 weeks could discriminate both American College of Rheumatology criteria for 50% improvement responses (P = 0.03) and DAS28-CRP improvement (P = 0.002). Changes in the MBDA score at 2 weeks were also associated with subsequent DAS28-CRP response (P = 0.02). Conclusion Our findings establish the criterion and discriminant validity of a novel multibiomarker test as an objective measure of RA disease activity to aid in the management of RA in patients with this condition. PMID:22736476

Physical activity and diabetes mellitus.

PubMed

Bhaskarabhatla, Krishna V; Birrer, Richard

2005-01-01

Diabetes mellitus (DM), a metabolic syndrome consisting of two main groups, type 1 and 2, is characterized by absolute or relative insulin deficiency or insulin resistance. Individuals with DM take part in physical activity for health promotion, disease management, and or recreational or competitive sports. Several studies confirm the beneficial role of physical activity in favorably altering the prognosis of DM. Exercise as a therapeutic strategy has potential risks, too. Hence, sports medicine physicians caring for athletes with diabetes have several important responsibilities. Diabetic education; pre-participatory evaluation for vascular, neurological, retinal or joint disease; diabetic status and control; promotion of blood glucose self-monitoring; and individualized dietary, medication, and physical activity plans are essential to achieve safe and enjoyable outcomes in individuals with diabetes who are embarking on physical activity.

Delays in Initiation of Disease-Modifying Therapy in Rheumatoid Arthritis Patients: Data from a US-Based Registry.

PubMed

Pappas, Dimitrios A; Kent, Jeffrey D; Greenberg, Jeffrey D; Mason, Marc A; Kremer, Joel M; Holt, Robert J

2015-12-01

The goal of this study was to evaluate how frequently rheumatoid arthritis (RA) therapy is instituted promptly and to describe the characteristics of patients who are not treated early upon diagnosis. The percentage of patients who at the time of enrollment in the Corrona registry were not receiving any RA-directed therapy was evaluated and their characteristics were summarized. The time to subsequent initiation of any RA-directed therapy was also estimated. Among 35,485 patients enrolled in Corrona, 34,735 (97.9%) were on appropriate therapy for RA and 750 (2.1%) had no history of any RA-directed therapy at time of enrollment. Among patients without any history of RA-directed therapy, the overall disease duration was 5.5 ± 9.0 years, with only 50.7% of patients having early disease (duration ≤1 year). Patients with no history of directed RA therapy did not have lower disease activity at enrollment compared with those receiving therapy. Clinical Disease Activity Index (CDAI) was 18.3 ± 15.0; 34% of patients had high and 27.6% moderate disease activity by CDAI. Patients were followed for a median (95% CI) time of 29.5 months (24.6-33.8). During the follow-up period, 372 out of 750 (49.6%) patients initiated RA-directed therapy. The median time to initiation of any RA-directed therapy was 12.1 months (95% CI 9.3-14.8). In this registry analysis, approximately 98% of patients were on appropriate RA therapy for their RA. However, a minority of patients with RA did not have a history of receiving disease-modifying therapy within a mean of approximately 5 years of RA onset and approximately 50% of them did not initiate any therapy within 12 months of registry follow-up. This delay in therapy did not appear to be related to a better controlled, or lower, RA disease activity state at the time of enrollment in the registry. Corrona, LLC.

Pre-Participation Medical Evaluation for Adventure and Wilderness Watersports.

PubMed

Nathanson, Andrew T; Young, Justin Mark J; Young, Craig

2015-12-01

A request for a preparticipation medical evaluation for wilderness watersports may be made by guiding agencies, instructional camps, or by patients presenting for an annual visit. Although guidelines have been published regarding preparticipation physical evaluation for traditional competitive high school and collegiate sports, little has been written about medical evaluations for those wishing to engage in wilderness and adventure watersports. in this article, we offer guidance based on literature review and expert opinion. Watersports are among the most common recreational activities in the United states and are generally safe. Drowning, however, is a significant risk, particularly in small, self-propelled craft, and among children. Medical counseling before participation in watersports should include screening for medical conditions which may impair swimming ability, including a history of seizures, heart disease, and lung disease. Physicians should also promote preventive health measures such as use of lifejackets and sun protection, as well as alcohol avoidance. Swim testing tailored to specific activities should be strongly considered for children and those with questionable swimming ability. Copyright © 2015. Published by Elsevier Inc.

Plants of Brazilian restingas with tripanocide activity against Trypanosoma cruzi strains.

PubMed

Faria, Robson Xavier; Souza, André Luis Almeida; Lima, Barbara; Tietbohl, Luis Armando Candido; Fernandes, Caio Pinho; Amaral, Raquel Rodrigues; Ruppelt, Bettina Monika; Santos, Marcelo Guerra; Rocha, Leandro

2017-12-01

Chagas disease is caused by the Trypanosoma cruzi affecting millions of people, and widespread throughout Latin America. This disease exhibits a problematic chemotherapy. Benznidazole, which is the drug currently used as standard treatment, lamentably evokes several adverse reactions. Among other options, natural products have been tested to discover a novel therapeutic drug for this disease. A lot of plants from the Brazilian flora did not contain studies about their biological effects. Restinga de Jurubatiba from Brazil is a sandbank ecosystem poorly studied in relation to plant biological activity. Thus, three plant species from Restinga de Jurubatiba were tested against in vitro antiprotozoal activity. Among six extracts obtained from leaves and stem parts and 2 essential oils derived from leave parts, only 3 extracts inhibited epimastigote proliferation. Substances present in the extracts with activity were isolated (quercetin, myricetin, and ursolic acid), and evaluated in relation to antiprotozoal activity against epimastigote Y and Dm28 Trypanosoma cruzi strains. All isolated substances were effective to reduce protozoal proliferation. Essentially, quercetin and myricetin did not cause mammalian cell toxicity. In summary, myricetin and quercetin molecule can be used as a scaffold to develop new effective drugs against Chagas's disease.

Juvenile idiopathic arthritis activity and function ability: deleterious effects in periodontal disease?

PubMed

Pugliese, Camila; van der Vinne, Roberta T A; Campos, Lucia M A; Guardieiro, Priscila R; Saviolli, Cynthia; Bonfá, Eloisa; Pereira, Rosa M R; Viana, Vilma S; Borba, Eduardo F; Silva, Clovis A

2016-01-01

The impact of juvenile idiopathic arthritis (JIA) in periodontal diseases is controversial probably due to gender and age heterogeneity. We therefore evaluated a homogeneous female post-pubertal JIA population for these conditions. Thirty-five JIA patients and 35 gender/age comparable healthy controls were evaluated according to demographic data, complete periodontal evaluation, fasting lipoproteins, and anti-lipoprotein lipase antibodies. JIA scores, laboratorial tests, X-rays, and treatment were also assessed. Current age was similar in JIA patients and controls (11.90 ± 2.0 vs. 12.50 ± 3.0 years, p = 0.289). Complete periodontal assessments revealed that gingival index, dental plaque, gingival bleeding, and clinical dental attachment indices were alike in JIA patients and controls (p > 0.05), except for gingival enlargement in former group (p < 0.0001). Further analysis of patients with and without gingivitis revealed that cyclosporine use was more often observed in JIA patients with gingivitis (37 vs. 0%, p = 0.01), whereas no differences were evidenced in demographic, JIA scores, inflammatory markers, and lipid profile in both groups. Of note, two parameters of periodontal assessment were correlated with JIA scores [gingival index (GI) and Childhood Health Assessment Questionnaire (CHAQ) (r s  = +0.402, p = 0.020)] and plaque index (PI) and visual analog scale (VAS) physician (r s  = +0.430, p = 0.013). In addition, evaluation of dental assessment demonstrated that JIA activity scores had positive correlation with decayed, missing, and filled teeth (DMF-T) and junvenile athritis disease activity score (JADAS) (r s  = +0.364,p = 0.037), VAS physician (r s  = +0.401,p = 0.021) and VAS patient (r s  = +0.364,p = 0.037). We demonstrated, using rigorous criteria, that periodontal and dental condition in JIA is similar to controls. In spite of that, the finding of a correlation with disease parameters provides additional evidence that increased activity and reduced functional ability underlies the deleterious effect of JIA in oral health.

Evaluation of CD44 and CD133 as markers of liver cancer stem cells in Egyptian patients with HCV-induced chronic liver diseases versus hepatocellular carcinoma

PubMed Central

Rozeik, Mohammed Saeed; Hammam, Olfat Ali; Ali, Ali Ibrahim; Magdy, Mona; Khalil, Heba; Anas, Amgad; Abo el Hassan, Ahmed Abdelaleem; Rahim, Ali Abdel; El-Shabasy, Ahmed Ibrahim

2017-01-01

Background Cancer stem cells (CSCs) play a critical role in tumor development, progression, metastasis and recurrence. Aim To evaluate hepatic expression of CD44 and CD133 in Egyptian patients with HCV-induced chronic liver diseases and hepatocellular carcinomas (HCCs), and to assess its correlation with inflammatory activity scores, stages of fibrosis (in chronic hepatitis with or without cirrhosis) and grades of HCC. Methods This prospective case-control study was conducted on eighty subjects who attended the Tropical Diseases Department, Al-Azhar University Hospital, and in collaboration with Theodor Bilharz Research Institute (2014–2016). They were divided as follows: A) Control healthy group: Ten individuals with serologically negative HCV-Ab and HBsAg, and histopathologically normal liver, B) Seventy patients subdivided into 3 groups; Twenty subjects each, as: HCV-Ab+ non-cirrhotic, HCV-Ab+ cirrhotic and HCC. Necroinflammatory activity and fibrosis in non-neoplastic liver biopsies were scored according to the METAVIR scoring system. CD44 and CD133 immunostaining was evaluated in all groups semi-quantitatively using H score. Statistical analysis was performed by SPSS version 22, using independent-samples t-test. Results Our study showed a significant increase of mean CD44 & CD133 expression values with disease progression among the groups (p<0.05). Their expressions increased significantly with the inflammatory activity scores and stages of fibrosis, reaching the highest values in A3F4 score compared to A1F1 (p<0.05). Moreover, there was a significant increase of their expressions across HCC grades (p<0.05), however with no significant correlation with focal lesions size. Conclusion CSCs clusters exhibiting CD133+ and/or CD44+ profiles were identified in chronic hepatitis, liver cirrhosis and HCC. CD133 and CD44 expressions significantly corresponded to the increased inflammatory activity, fibrosis stages and higher tumor grades. Therefore, evaluation of CD44 and CD133 expression profiles as CSCs markers in non-neoplastic liver and HCCs can help in development of novel therapeutic agents for HCC targeting and prevention. PMID:28894525

Serum levels of macrophage migration inhibitory factor are associated with rheumatoid arthritis course.

PubMed

Llamas-Covarrubias, Mara Anaís; Valle, Yeminia; Navarro-Hernández, Rosa Elena; Guzmán-Guzmán, Iris Paola; Ramírez-Dueñas, María Guadalupe; Rangel-Villalobos, Héctor; Estrada-Chávez, Ciro; Muñoz-Valle, José Francisco

2012-08-01

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease of unknown etiology. Many cytokines have been found to be associated with RA pathogenesis and among them is macrophage migration inhibitory factor (MIF). The aim of this study was to determine whether MIF serum levels are associated with RA course, clinical activity, and clinical biomarkers of the disease. MIF levels were determined in serum samples of 54 RA patients and 78 healthy subjects (HS) by enzyme-linked immunosorbent assay (ELISA). Disease activity was evaluated using the DAS28 score. Patients were subgrouped according to disease activity and years of evolution of disease. Statistical analysis was carried out by SPSS 10.0 and GraphPad Prism 5 software. RA patients presented increased levels of MIF as compared to HS. MIF levels were raised on early stages of RA and tend to decrease according to years of evolution. Moreover, MIF levels positively correlated with rheumatoid factor in RA patients and with C reactive protein in all individuals studied. Our findings suggest that MIF plays a role in early stages of RA.

A grid for a precise analysis of daily activities.

PubMed

Wojtasik, V; Olivier, C; Lekeu, F; Quittre, A; Adam, S; Salmon, E

2010-01-01

Assessment of daily living activities is essential in patients with Alzheimer's disease. Most current tools quantitatively assess overall ability but provide little qualitative information on individual difficulties. Only a few tools allow therapists to evaluate stereotyped activities and record different types of errors. We capitalised on the Kitchen Activity Assessment to design a widely applicable analysis grid that provides both qualitative and quantitative data on activity performance. A cooking activity was videotaped in 15 patients with dementia and assessed according to the different steps in the execution of the task. The evaluations obtained with our grid showed good correlations between raters, between versions of the grid and between sessions. Moreover, the degree of independence obtained with our analysis of the task correlated with the Kitchen Activity Assessment score and with a global score of cognitive functioning. We conclude that assessment of a daily living activity with this analysis grid is reproducible and relatively independent of the therapist, and thus provides quantitative and qualitative information useful for both evaluating and caring for demented patients.

In-Vitro, Anti-Bacterial Activities of Aqueous Extracts of Acacia catechu (L.F.)Willd, Castanea sativa, Ephedra sinica stapf and shilajita mumiyo Against Gram Positive and Gram Negative Bacteria

PubMed Central

Dashtdar, Mehrab; Dashtdar, Mohammad Reza; Dashtdar, Babak; shirazi, Mohammad khabaz; Khan, Saeed Ahmad

2013-01-01

Objective: Evaluations of the in-vitro anti-bacterial activities of aqueous extracts of Acacia catechu (L.F.)Willd, Castanea sativa, Ephedra sinica stapf and Shilajita mumiyo against gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumonia) and gram-negative bacteria (Escherichia coli, klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa) are reasonable since these ethnomedicinal plants have been used in Persian folk medicine for treating skin diseases, venereal diseases, respiratory problems and nervous disorders for ages. Methods: The well diffusion method (KB testing) with a concentration of 250 μg/disc was used for evaluating the minimal inhibitory concentrations (MIC). Maximum synergistic effects of different combinations of components were also observed. Results: A particular combination of Acacia catechu (L.F.) Willd, Castanea sativa, Ephedra sinica stapf and shilajita mumiyo extracts possesses an outstanding anti-bacterial activity. It's inhibiting effect on microorganisms is significant when compared to the control group (P< 0.05). Staphylococcus aureus was the most sensitive microorganism. The highest antibacterial activity against gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumonia) or gram-negative bacteria (Escherichia coli, Klebsiella pneumonia, Proteus mirabilis and Pseudomonas aeruginosa) was exerted by formula number 2 (Table1). Conclusion: The results reveal the presence of antibacterial activities of Acacia catechu, Castanea sativa husk, Ephedra sp. and Mumiyo against gram-positive and gram-negative bacteria. Synergistic effects in a combined formula, especially in formula number 2 (ASLANⓇ) can lead to potential sources of new antiseptic agents for treatment of acute or chronic skin ulcers. These results considering the significant antibacterial effect of the present formulation, support ethno-pharmacological uses against diarrheal and venereal diseases and demonstrate use of these plants to treat infectious diseases. PMID:25780663

Potent anti-inflammatory effects of systemically-administered curcumin modulates periodontal disease in vivo

PubMed Central

Guimarães, Morgana R.; Coimbra, Leila S.; de Aquino, Sabrina Garcia; Spolidorio, Luis C.; Kirkwood, Keith L.; Junior, Carlos Rossa

2011-01-01

Background Curcumin is a plant-derived dietary spice with various biological activities, including anti-tumoral and anti-inflammatory. Its therapeutic applications have been studied in a variety of conditions, including rheumatoid arthritis, colon cancer and depression; but no studies evaluated the effects of curcumin on periodontal disease in vivo. Methods Experimental periodontal disease was induced in rats by placing cotton ligatures around both lower first molars. Curcumin was given to the rats intragastrically daily in two doses (30 and 100 mg/Kg) during 15 days. Control animals received ligatures but only the corn oil vehicle by gavage and no treatment negative control animals were included. Bone resorption was assessed by microcomputer tomography and the inflammatory status was evaluated by stereometric analysis. RT-qPCR and ELISA were used to determine the expression of interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and prostaglandin E2 (PGE2) synthase on the gingival tissues. Modulation of p38 mitogen-activated protein kinase (MAPK) and NK-kB activation was assessed by western blot. Results Bone resorption was effectively induced in the experimental period, but it was not affected by either dose of curcumin. Curcumin effectively inhibited cytokine gene expression at mRNA and protein levels and dose-dependently inhibited activation of NF-kB in the gingival tissues. p38 MAPK activation was not inhibited by curcumin. Curcumin-treated animals also presented a marked reduction on the inflammatory cell infiltrate and increased collagen content and fibroblastic cell numbers. Conclusions Curcumin did not prevent alveolar bone resorption, but its potent anti-inflammatory effect suggests it may have a therapeutic potential in periodontal diseases. PMID:21306385

A retrospective study of 77 cats with severe hepatic lipidosis: 1975-1990.

PubMed

Center, S A; Crawford, M A; Guida, L; Erb, H N; King, J

1993-01-01

The physical, clinicopathologic, and survival rates of 77 cats with severe spontaneous hepatic lipidosis are detailed in this report. Cats were subdivided into groups designated as idiopathic lipidosis if no other disease process was recognized, or secondary lipidosis if another disease process was diagnosed. Cats were also subdivided into groups designated as survivors or nonsurvivors on the basis of successful recuperation at 4 months after initial diagnosis. Differences between disease and survival groups were evaluated for significance. Overall, more female cats and middle-aged cats were affected. Presenting complaints of vomiting, anorexia, weakness, and weight loss were common. Physical assessment of most cats showed obvious hepatomegaly, jaundice, dehydration, and a weight loss > or = 25% of usual body weight. Neurobehavioral signs indicative of hepatic encephalopathy, other than ptyalism and depression, were rare. Clinicopathologic features are characterized by hyperbilirubinemia and increased activities of serum ALT, AST, and ALP, with only small if any increase in gamma GT activity. Clinical features distinguishing cats with hepatic lipidosis from those with other serious cholestatic disorders include absence of hyperglobulinemia and low gamma GT activity relative to ALP activity. Although coagulation tests were abnormal in 45% of cats tested (n = 44), few cats showed clinical bleeding tendencies. Most cats received prophylactic vitamin K1 therapy. Forty two cats received aggressive nutritional and supportive care and of these 55% survived. Cats with idiopathic disease were significantly younger, had significantly higher ALP activity and bilirubin concentration, and had a slightly better survival rate than cats with secondary lipidosis. Low PCV, hypokalemia, and an older age were significantly related to nonsurvival. Because of the variety of diets and food supplements used in case management, the influence of nutritional factors on survival could not be evaluated.

Obesity and rates of clinical remission and low MRI inflammation in rheumatoid arthritis.

PubMed

George, Michael D; Østergaard, Mikkel; Conaghan, Philip G; Emery, Paul; Baker, Daniel G; Baker, Joshua F

2017-10-01

Obesity has been proposed as a risk factor for refractory rheumatoid arthritis (RA). We evaluated the impact of obesity on achieving clinical and imaging definitions of low disease activity. This study evaluated 470 patients with RA from GO-BEFORE and GO-FORWARD randomised clinical trials. Included patients had blinded clinical disease activity measures and MRI at baseline, 24 and 52 weeks. Synovitis, osteitis and total inflammation scores were determined using the RA MRI scoring system. Multivariable logistic regression analyses compared odds of achieving Disease Activity Score using 28 joints and C-reactive protein (DAS28-CRP) remission, low component measures, or low MRI inflammation measures at 24 weeks in patients with obesity versus no obesity. At 24 weeks, patients with obesity were significantly less likely to achieve DAS28(CRP) remission (OR 0.47; 95% CI 0.24 to 0.92, p=0.03). In contrast, patients with obesity had similar odds of achieving low synovitis (OR 0.94; 95% CI 0.51 to 1.72, p=0.84) and inflammation scores (OR 1.16; 95% CI 0.61 to 2.22, p=0.64) and greater odds of achieving low osteitis scores (OR 2.06; 95% CI 1.10 to 3.84, p=0.02) versus normal weight patients. Patients with RA and obesity have lower rates of DAS28 remission but similar rates of low MRI activity compared with patients without obesity, suggesting that obesity and its associated comorbidities can bias clinical disease activity measures. NCT00361335 and NCT00264550; Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Running for your life: A review of physical activity and cardiovascular disease risk reduction in individuals with schizophrenia.

PubMed

Chalfoun, Claire; Karelis, Antony D; Stip, Emmanuel; Abdel-Baki, Amal

2016-08-01

Individuals with schizophrenia have a greater risk for cardiometabolic risk factors (e.g. central obesity, insulin resistance, hypertension and dyslipidaemia), cardiovascular diseases and mortality. This risky profile may be explained by the adverse effects of antipsychotic medications and an unhealthy lifestyle (e.g. smoking, poor nutrition and low physical activity). In the general population, physical activity has been shown to be the optimal strategy to improve both cardiometabolic parameters and cardiorespiratory fitness levels. Accordingly, an emerging literature of non-pharmacological interventions (e.g. cognitive behavioural therapy, diet and physical activity) has been studied in individuals with schizophrenia. Therefore, the purpose of this review was 1) to conduct a critical literature review of non-pharmacological interventions that included some kind of physical activity (including supervised and unsupervised exercise training) and target cardiometabolic risk factors in individuals with schizophrenia. 2) To describe the contribution of physical activity alone by reviewing trials of supervised exercise training programmes only. A literature review via systematic keyword search for publications in Medline, PubMed, Embase and PsycINFO was performed. Many non-pharmacological interventions are efficient in reducing cardiovascular disease risk factors when combined with physical activity. Supervised physical activity has been successful in decreasing cardiovascular disease risk, and aerobic interval training appears to provide more benefits by specifically targeting cardiorespiratory fitness levels. In conclusion, physical activity is an effective strategy for addressing cardiovascular disease risk in individuals with schizophrenia. Long-term studies are needed to evaluate the feasibility and impact of exercise training programmes in individuals with schizophrenia.

Patient-Reported Outcome Measures for Use in Clinical Trials and Clinical Practice in Inflammatory Bowel Diseases: A Systematic Review.

PubMed

de Jong, Marin J; Huibregtse, Roxanne; Masclee, Ad A M; Jonkers, Daisy M A E; Pierik, Marie J

2018-05-01

Mucosal inflammation must be carefully monitored to improve the long-term outcomes of patients with inflammatory bowel diseases (IBD). Patient-reported outcome measures (PROMs) are used increasingly to monitor disease activity in clinical practice and as endpoints in clinical trials. We performed a systematic review to provide an overview of the available PROMs on IBD activity and to evaluate their diagnostic value. A systematic search of the PubMed, Medline, Cochrane library, and Embase databases using defined keywords, identified 973 articles. These were screened by 2 independent reviewers, and 37 articles on development or validation of PROMs to assess IBD activity were identified for further analysis. Based on the recommendations of the Food and Drug Administration (FDA), the following measurement properties were evaluated: content, construct, and criterion validity; reliability; and responsiveness to change. In addition, data on ease of use in clinical practice were collected. Seventeen articles presenting 20 different PROMs were included the final analysis, although none met all the FDA-recommended criteria. Only 2 PROMs (patient-reported Harvey Bradshaw Index and Simple Clinical Colitis Activity Index scores) reported patient involvement during its development. Only 6 PROMs (patient-reported global assessment, patient assessment of disease activity, mobile health index for Crohn's disease, mobile health index for ulcerative colitis, patient-reported outcome derived from the Mayo score, and the 6-point Mayo score) were validated as markers of IBD activity, using findings from endoscopy as the reference standard; these PROMs identified patients with mucosal inflammation with area under the curve values of 0.63-0.82. The mobile health index for CD and UC scores had the best measurement properties for use in clinical practice and in clinical trials. In a systematic review, we identified more than 20 PROMS that have been developed and tested for their ability to determine IBD activity. Further studies are needed to determine their accuracy and whether they can be used effectively in routine practice, clinical trials, telemedicine systems, and value-based healthcare programs. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force

PubMed Central

Smolen, Josef S; Breedveld, Ferdinand C; Burmester, Gerd R; Bykerk, Vivian; Dougados, Maxime; Emery, Paul; Kvien, Tore K; Navarro-Compán, M Victoria; Oliver, Susan; Schoels, Monika; Scholte-Voshaar, Marieke; Stamm, Tanja; Stoffer, Michaela; Takeuchi, Tsutomu; Aletaha, Daniel; Andreu, Jose Louis; Aringer, Martin; Bergman, Martin; Betteridge, Neil; Bijlsma, Hans; Burkhardt, Harald; Combe, Bernard; Durez, Patrick; Fonseca, Joao Eurico; Gibofsky, Alan; Gomez-Reino, Juan J; Graninger, Winfried; Hannonen, Pekka; Haraoui, Boulos; Kouloumas, Marios; Landewe, Robert; Martin-Mola, Emilio; Nash, Peter; Ostergaard, Mikkel; Östör, Andrew; Richards, Pam; Sokka-Isler, Tuulikki; Thorne, Carter; Tzioufas, Athanasios G; van Vollenhoven, Ronald; de Wit, Martinus

2016-01-01

Background Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights. Objective To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion. Methods A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived. Results The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1–3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the disease, especially comorbidity and shared decision-making with the patient. Levels of evidence had increased for many items compared with the 2010 recommendations, and levels of agreement were very high for most of the individual recommendations (≥9/10). Conclusions The 4 overarching principles and 10 recommendations are based on stronger evidence than before and are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA. PMID:25969430

Accelerometry-based monitoring of daily physical activity in children with juvenile idiopathic arthritis.

PubMed

Nørgaard, M; Twilt, M; Andersen, L B; Herlin, T

2016-01-01

Juvenile idiopathic arthritis (JIA) may cause functional impairment, reduced participation in physical activity (PA) and, over time, physical deconditioning. The aim of this study was to objectively monitor daily free-living PA in 10-16-year-old children with JIA using accelerometry with regard to disease activity and physical variables and to compare the data with those from healthy age- and gender-matched controls. Patients underwent an evaluation of disease activity, functional ability, physical capacity, and pain. Accelerometer monitoring was assessed using the GT1M ActiGraph. Normative data from two major studies on PA in Danish schoolchildren were used for comparison. Data of accelerometry were available for 61 JIA patients and 2055 healthy controls. Of the JIA patients, 57% showed below-average values of maximal physical capacity (fitness level). JIA patients showed low disease activity and pain and were physically well functioning. Accelerometer counts were lower in JIA patients than in controls. Accelerometer measurements were negatively correlated with disease activity, erythrocyte sedimentation rate (ESR), and number of joints with swelling and/or limited range of motion (ROM). No correlation was found between PA and pain scores, functional ability, and hypermobility. Patients with involvement of ankles or hips demonstrated significantly lower levels of PA. Children with JIA are less physically active and have lower physical capacity and fitness than their age- and gender-matched healthy peers despite good disease control. The involvement of hips or ankles is associated with lower PA.

Inverse associations of outdoor activity and vitamin D intake with the risk of Parkinson's disease.

PubMed

Zhu, Dan; Liu, Gui-you; Lv, Zheng; Wen, Shi-rong; Bi, Sheng; Wang, Wei-zhi

2014-10-01

Early studies had suggested that vitamin D intake was inversely associated with neurodegenerative diseases, such as Alzheimer's disease and multiple sclerosis. However, the associations of vitamin D intake and outdoor activities with Parkinson's disease (PD) are still unclear, so this study is to evaluate these relationships from a case-control study in elderly Chinese. The study population involved 209 cases with new onsets of PD and 210 controls without neurodegenerative diseases. The data on dietary vitamin D and outdoor activities were collected using a food-frequency questionnaire and self-report questionnaire. Multivariable logistic regressions were used to examine the associations between dietary outdoor activities, vitamin D intake and PD. Adjustment was made for sex, age, smoking, alcohol use, education, and body mass index (BMI). Adjusted odds ratios (ORs) for PD in quartiles for outdoor physical activity were 1 (reference), 0.739 (0.413, 1.321), 0.501 (0.282, 0.891), and 0.437 (0.241, 0.795), respectively (P=0.002 for trend). Adjusted ORs for PD in quartiles for total vitamin D intake were 1 (reference), 0.647 (0.357, 1.170), 0.571 (0.318, 1.022), and 0.538 (0.301, 0.960), respectively (P=0.011 for trend). Our study suggested that outdoor activity and total vitamin D intake were inversely associated with PD, and outdoor activity seems to be more significantly associated with decreased risk for PD.

Role of antibiotics for treatment of inflammatory bowel disease

PubMed Central

Nitzan, Orna; Elias, Mazen; Peretz, Avi; Saliba, Walid

2016-01-01

Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn’s disease (CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms. Antibiotics show a clinical benefit when used for the treatment of pouchitis. The downsides of antibiotic treatment, especially with recurrent or prolonged courses such as used in inflammatory bowel disease, are significant side effects that often cause intolerance to treatment, Clostridium dificile infection, and increasing antibiotic resistance. More studies are needed to define the exact role of antibiotics in inflammatory bowel diseases. PMID:26811648

Role of antibiotics for treatment of inflammatory bowel disease.

PubMed

Nitzan, Orna; Elias, Mazen; Peretz, Avi; Saliba, Walid

2016-01-21

Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn's disease (CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms. Antibiotics show a clinical benefit when used for the treatment of pouchitis. The downsides of antibiotic treatment, especially with recurrent or prolonged courses such as used in inflammatory bowel disease, are significant side effects that often cause intolerance to treatment, Clostridium dificile infection, and increasing antibiotic resistance. More studies are needed to define the exact role of antibiotics in inflammatory bowel diseases.

Could Sodium Chloride be an Environmental Trigger for Immune-Mediated Diseases? An Overview of the Experimental and Clinical Evidence

PubMed Central

Toussirot, Eric; Béreau, Matthieu; Vauchy, Charline; Saas, Philippe

2018-01-01

Immune mediated diseases (IMDs) are complex chronic inflammatory diseases involving genetic and environmental factors. Salt intake has been proposed as a diet factor that can influence the immune response. Indeed, experimental data report the influence of sodium chloride on the differentiation of naive CD4+ T cells into IL-17 secreting T helper (Th) cells (Th17 cells), by a mechanism involving the serum glucocorticoid kinase-1 (SGK1) that promotes the expression of the IL-23 receptor (IL-23R). The IL-23/IL-23R is critical for pathogenic inflammatory Th17 cell differentiation. Experimental data in murine models of arthritis, colitis and encephalomyelitis corroborate these findings. This manuscript reviews the current knowledge on the effects of sodium chloride on innate and adaptive immunity. We also performed a systematic literature review for clinical studies examining the relationships between salt consumption and the development or the activity/severity of the most common IMDs mediated by the IL-23/Th17 pathway, i.e., rheumatoid arthritis (RA), multiple sclerosis (MS), and Crohn's disease (CD). Nine studies were found, 4 in RA, 4 in MS and 1 in CD. An association was found between developments of anti-citrullinated protein antibody (ACPA) positive RA in smokers and salt intake, but these results were not confirmed in another study. For MS, no association was observed in pediatric subjects while in adult patients, a link was found between salt intake and disease activity. However, this result was not confirmed in another study. These conflicting results highlight the fact that further evaluation in human IMDs is required. Moreover, physicians need to develop clinical trials with diet interventions to evaluate the impact of low salt intake on disease activity/severity of IMDs. PMID:29740348

Could Sodium Chloride be an Environmental Trigger for Immune-Mediated Diseases? An Overview of the Experimental and Clinical Evidence.

PubMed

Toussirot, Eric; Béreau, Matthieu; Vauchy, Charline; Saas, Philippe

2018-01-01

Immune mediated diseases (IMDs) are complex chronic inflammatory diseases involving genetic and environmental factors. Salt intake has been proposed as a diet factor that can influence the immune response. Indeed, experimental data report the influence of sodium chloride on the differentiation of naive CD4 + T cells into IL-17 secreting T helper (Th) cells (Th17 cells), by a mechanism involving the serum glucocorticoid kinase-1 (SGK1) that promotes the expression of the IL-23 receptor (IL-23R). The IL-23/IL-23R is critical for pathogenic inflammatory Th17 cell differentiation. Experimental data in murine models of arthritis, colitis and encephalomyelitis corroborate these findings. This manuscript reviews the current knowledge on the effects of sodium chloride on innate and adaptive immunity. We also performed a systematic literature review for clinical studies examining the relationships between salt consumption and the development or the activity/severity of the most common IMDs mediated by the IL-23/Th17 pathway, i.e., rheumatoid arthritis (RA), multiple sclerosis (MS), and Crohn's disease (CD). Nine studies were found, 4 in RA, 4 in MS and 1 in CD. An association was found between developments of anti-citrullinated protein antibody (ACPA) positive RA in smokers and salt intake, but these results were not confirmed in another study. For MS, no association was observed in pediatric subjects while in adult patients, a link was found between salt intake and disease activity. However, this result was not confirmed in another study. These conflicting results highlight the fact that further evaluation in human IMDs is required. Moreover, physicians need to develop clinical trials with diet interventions to evaluate the impact of low salt intake on disease activity/severity of IMDs.

Changing clinical patterns in rheumatoid arthritis management over two decades: sequential observational studies.

PubMed

Mian, Aneela N; Ibrahim, Fowzia; Scott, Ian C; Bahadur, Sardar; Filkova, Maria; Pollard, Louise; Steer, Sophia; Kingsley, Gabrielle H; Scott, David L; Galloway, James

2016-01-27

Rheumatoid arthritis (RA) treatment paradigms have shifted over the last two decades. There has been increasing emphasis on combination disease modifying anti-rheumatic drug (DMARD) therapy, newer biologic therapies have become available and there is a greater focus on achieving remission. We have evaluated the impact of treatment changes on disease activity scores for 28 joints (DAS28) and disability measured by the health assessment questionnaire scores (HAQ). Four cross-sectional surveys between 1996 and 2014 in two adjacent secondary care rheumatology departments in London evaluated changes in drug therapy, DAS28 and its component parts and HAQ scores (in three surveys). Descriptive statistics used means and standard deviations (SD) or medians and interquartile ranges (IQR) to summarise changes. Spearman's correlations assessed relationships between assessments. 1324 patients were studied. Gender ratios, age and mean disease duration were similar across all cohorts. There were temporal increases in the use of any DMARDs (rising from 61% to 87% of patients from 1996-2014), combination DMARDs (1% to 41%) and biologic (0 to 32%). Mean DAS28 fell (5.2 to 3.7), active disease (DAS28 > 5.1) declined (50% to 18%) and DAS28 remission (DAS28 < 2.6) increased (8% to 28%). In contrast HAQ scores were unchanged (1.30 to 1.32) and correlations between DAS28 and HAQ weakened (Spearman's rho fell from 0.56 to 0.44). Treatment intensity has increased over time, disease activity has fallen and there are more remissions. However, these improvements in controlling synovitis have not resulted in comparable reductions in disability measured by HAQ. As a consequence the relationship between DAS28 and HAQ has become weaker over time. Although the reasons for this divergence between disease activity and disability are uncertain, focussing treatment entirely in suppressing synovitis may be insufficient.

Efficacy and safety of flavocoxid compared with naproxen in subjects with osteoarthritis of the knee- a subset analysis.

PubMed

Levy, Robert; Khokhlov, Alexander; Kopenkin, Sergey; Bart, Boris; Ermolova, Tatiana; Kantemirova, Raiasa; Mazurov, Vadim; Bell, Marjorie; Caldron, Paul; Pillai, Lakshmi; Burnett, Bruce

2010-12-01

twice-daily flavocoxid, a cyclooxygenase and 5-lipoxygenase inhibitor with potent antioxidant activity of botanical origin, was evaluated for 12 weeks in a randomized, double-blind, active-comparator study against naproxen in 220 subjects with moderate-severe osteoarthritis (OA) of the knee. As previously reported, both groups noted a significant reduction in the signs and symptoms of OA with no detectable differences in efficacy between the groups when the entire intent-to-treat population was considered. This post-hoc analysis compares the efficacy of flavocoxid to naproxen in different subsets of patients, specifically those related to age, gender, and disease severity as reported at baseline for individual response parameters. in the original randomized, double-blind study, 220 subjects were assigned to receive either flavocoxid (500 mg twice daily) or naproxen (500 mg twice daily) for 12 weeks. In this subgroup analysis, primary outcome measures including the Western Ontario and McMaster Universities OA index and subscales, timed walk, and secondary efficacy variables, including investigator global assessment for disease and global response to treatment, subject visual analog scale for discomfort, overall disease activity, global response to treatment, index joint tenderness and mobility, were evaluated for differing trends between the study groups. subset analyses revealed some statistically significant differences and some notable trends in favor of the flavocoxid group. These trends became stronger the longer the subjects continued on therapy. These observations were specifically noted in older subjects (>60 years), males and in subjects with milder disease, particularly those with lower subject global assessment of disease activity and investigator global assessment for disease and faster walking times at baseline. initial analysis of the entire intent-to-treat population revealed that flavocoxid was as effective as naproxen in managing the signs and symptoms of OA of the knee. Detailed analyses of subject subsets demonstrated distinct trends in favor of flavocoxid for specific groups of subjects.

Criterion Validation Testing of Clinical Metrology Instruments for Measuring Degenerative Joint Disease Associated Mobility Impairment in Cats

PubMed Central

Gruen, Margaret E.; Griffith, Emily H.; Thomson, Andrea E.; Simpson, Wendy; Lascelles, B. Duncan X.

2015-01-01

Introduction Degenerative joint disease and associated pain are common in cats, particularly in older cats. There is a need for treatment options, however evaluation of putative therapies is limited by a lack of suitable, validated outcome measures that can be used in the target population of client owned cats. The objectives of this study were to evaluate low-dose daily meloxicam for the treatment of pain associated with degenerative joint disease in cats, and further validate two clinical metrology instruments, the Feline Musculoskeletal Pain Index (FMPI) and the Client Specific Outcome Measures (CSOM). Methods Sixty-six client owned cats with degenerative joint disease and owner-reported impairments in mobility were screened and enrolled into a double-masked, placebo-controlled, randomized clinical trial. Following a run-in baseline period, cats were given either placebo or meloxicam for 21 days, then in a masked washout, cats were all given placebo for 21 days. Subsequently, cats were given the opposite treatment, placebo or meloxicam, for 21 days. Cats wore activity monitors throughout the study, owners completed clinical metrology instruments following each period. Results Activity counts were increased in cats during treatment with daily meloxicam (p<0.0001) compared to baseline. The FMPI results and activity count data offer concurrent validation for the FMPI, though the relationship between baseline activity counts and FMPI scores at baseline was poor (R2=0.034). The CSOM did not show responsiveness for improvement in this study, and the relationship between baseline activity counts and CSOM scores at baseline was similarly poor (R2=0.042). Conclusions Refinements to the FMPI, including abbreviation of the instrument and scoring as percent of possible score are recommended. This study offered further validation of the FMPI as a clinical metrology instrument for use in detecting therapeutic efficacy in cats with degenerative joint disease. PMID:26162101

Alcoholic liver disease patients' perspective of a coping and physical activity-oriented rehabilitation intervention after hepatic encephalopathy.

PubMed

Mikkelsen, Maria Rudkjaer; Hendriksen, Carsten; Schiødt, Frank Vinholt; Rydahl-Hansen, Susan

2016-09-01

To identify and describe the impact of a coping and physical activity-oriented rehabilitation intervention on alcoholic liver disease patients after hepatic encephalopathy in terms of their interaction with professionals and relatives. Patients who have experienced alcohol-induced hepatic encephalopathy have reduced quality of life, multiple complications, and social problems, and rehabilitation opportunities for these patients are limited. A grounded theory study and an evaluation study of a controlled intervention study. Semi-structured interviews were conducted with 10 alcoholic liver disease patients who were diagnosed with hepatic encephalopathy and participated in a coping and physical activity-oriented rehabilitation intervention. Richard S. Lazarus's theory of stress and coping inspired the interview guide. The significance of a coping and physical activity-oriented rehabilitation intervention on alcoholic liver disease patients' ability to cope with problems after surviving alcohol-induced hepatic encephalopathy in terms of their interaction with professionals and relatives was characterised by the core category 'regain control over the diseased body'. This is subdivided into three separate categories: 'the experience of being physically strong', 'togetherness' and 'self-control', and they impact each other and are mutually interdependent. Alcoholic liver disease patients described the strength of the rehabilitation as regaining control over the diseased body. Professionals and relatives of patients with alcoholic liver disease may need to focus on strengthening and preserving patients' control of their diseased body by facilitating the experience of togetherness, self-control and physical strength when interacting with and supporting patients with alcoholic liver disease. A coping and physical activity-oriented rehabilitation intervention may help alcoholic liver disease patients to regain control over their diseased body and give patients the experience of togetherness, self-control and physical strength. Professionals should be aware of giving the patients the experience of togetherness in their interactions, help them perceive self-control and gain physical strength during their rehabilitation. © 2016 John Wiley & Sons Ltd.

Thioesters for the in vitro evaluation of agents to image brain cholinesterases.

PubMed

Macdonald, Ian R; Jollymore, Courtney T; Reid, G Andrew; Pottie, Ian R; Martin, Earl; Darvesh, Sultan

2013-06-01

Cholinesterases are associated with pathology characteristic of conditions such as Alzheimer's disease and are therefore, considered targets for neuroimaging. Ester derivatives of N-methylpiperidinol are promising potential imaging agents; however, methodology is lacking for evaluating these compounds in vitro. Here, we report the synthesis and evaluation of a series of N-methylpiperidinyl thioesters, possessing comparable properties to their corresponding esters, which can be directly evaluated for cholinesterase kinetics and histochemical distribution in human brain tissue. N-methylpiperidinyl esters and thioesters were synthesized and they demonstrated comparable cholinesterase kinetics. Furthermore, thioesters were capable, using histochemical method, to visualize cholinesterase activity in human brain tissue. N-methylpiperidinyl thioesters can be rapidly evaluated for cholinesterase kinetics and visualization of enzyme distribution in brain tissue which may facilitate development of cholinesterase imaging agents for application to conditions such as Alzheimer's disease.

Role of Biomarkers in Diagnosis and Prognostic Evaluation of Acute Pancreatitis

PubMed Central

Meher, Susanta; Mishra, Tushar Subhadarshan; Sasmal, Prakash Kumar; Rath, Satyajit; Sharma, Rakesh; Rout, Bikram; Sahu, Manoj Kumar

2015-01-01

Acute pancreatitis is a potentially life threatening disease. The spectrum of severity of the illness ranges from mild self-limiting disease to a highly fatal severe necrotizing pancreatitis. Despite intensive research and improved patient care, overall mortality still remains high, reaching up to 30–40% in cases with infected pancreatic necrosis. Although little is known about the exact pathogenesis, it has been widely accepted that premature activation of digestive enzymes within the pancreatic acinar cell is the trigger that leads to autodigestion of pancreatic tissue which is followed by infiltration and activation of leukocytes. Extensive research has been done over the past few decades regarding their role in diagnosis and prognostic evaluation of severe acute pancreatitis. Although many standalone biochemical markers have been studied for early assessment of severity, C-reactive protein still remains the most frequently used along with Interleukin-6. In this review we have discussed briefly the pathogenesis and the role of different biochemical markers in the diagnosis and severity evaluation in acute pancreatitis. PMID:26345247

Germacranolide-type sesquiterpene lactones from Smallanthus sonchifolius with promising activity against Leishmania mexicana and Trypanosoma cruzi.

PubMed

Ulloa, Jerónimo L; Spina, Renata; Casasco, Agustina; Petray, Patricia B; Martino, Virginia; Sosa, Miguel A; Frank, Fernanda M; Muschietti, Liliana V

2017-11-13

Leishmaniasis and Chagas disease are life-threatening illnesses caused by the protozoan parasites Leishmania spp. and Trypanosoma cruzi, respectively. They are known as "neglected diseases" due to the lack of effective drug treatments and the scarcity of research work devoted to them. Therefore, the development of novel and effective drugs is an important and urgent need. Natural products are an important source of bioactive molecules for the development of new drugs. In this study, we evaluated the activity of enhydrin, uvedalin and polymatin B, three sesquiterpene lactones (STLs) isolated from Smallanthus sonchifolius, on Leishmania mexicana (MNYC/BZ/62/M) and Trypanosoma cruzi (Dm28c). In addition, the in vivo trypanocidal activity of enhydrin and uvedalin and the effects of these STLs on parasites' ultrastructure were evaluated. The inhibitory effect of the three STLs on the growth of L. mexicana amastigotes and promastigotes as well as T. cruzi epimastigotes was evaluated in vitro. The changes produced by the STLs on the ultrastructure of parasites were examined by transmission electron microscopy (TEM). Enhydrin and uvedalin were also studied in a murine model of acute T. cruzi infection (RA strain). Serum activities of the hepatic enzymes alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were used as biochemical markers of hepatotoxicity. The three compounds exhibited leishmanicidal activity on both parasite forms with IC 50 values of 0.42-0.54 μg/ml for promastigotes and 0.85-1.64 μg/ml for intracellular amastigotes. Similar results were observed on T. cruzi epimastigotes (IC 50 0.35-0.60 μg/ml). The TEM evaluation showed marked ultrastructural alterations, such as an intense vacuolization and mitochondrial swelling in both L. mexicana promastigotes and T. cruzi epimastigotes exposed to the STLs. In the in vivo study, enhydrin and uvedalin displayed a significant decrease in circulating parasites (50-71%) and no signs of hepatotoxicity were detected. Enhydrin, uvedalin and polymatin B possess significant leishmanicidal and trypanocidal activity on different parasite stages. These results show that these compounds may provide valuable leads for the development of new drugs against these neglected parasitic diseases.

Diffusion-weighted imaging for evaluating inflammatory activity in Crohn's disease: comparison with histopathology, conventional MRI activity scores, and faecal calprotectin.

PubMed

Pendsé, D A; Makanyanga, J C; Plumb, A A; Bhatnagar, G; Atkinson, D; Rodriguez-Justo, Manuel; Halligan, S; Taylor, S A

2017-01-01

To evaluate whether the extent of enteric diffusion-weighted imaging (DWI) signal abnormality reflects inflammatory burden in Crohn's disease (CD), and to compare qualitative and quantitative grading. 69 CD patients (35 male, age 16-78) undergoing MR enterography with DWI (MRE-D) and the same-day faecal calprotectin (cohort 1) were supplemented by 29 patients (19 male, age 16-70) undergoing MRE-D and terminal ileal biopsy (cohort 2). Global (cohort 1) and terminal ileal (cohort 2) DWI signal was graded (0 to 3) by 2 radiologists and segmental apparent diffusion coefficient (ADC) calculated. Data were compared to calprotectin and a validated MRI activity score [MEGS] (cohort 1), and a histopathological activity score (eAIS) (cohort 2) using nonparametric testing and rank correlation. Patients with normal (grades 0 and 1) DWI signal had lower calprotectin and MEGS than those with abnormal signal (grades 2 and 3) (160 vs. 492 μg/l, p = 0.0004, and 3.3 vs. 21, p < 0.0001), respectively. Calprotectin was lower if abnormal DWI affected <10 cm of small bowel compared to diffuse small and large bowel abnormality (236 vs. 571 μg, p = 0.009). The sensitivity and specificity for active disease (calprotectin > 120 μg/l) were 83% and 52%, respectively. There was a negative correlation between ileal MEGS and ADC (r = -0.41, p = 0.017). There was no significant difference in eAIS between qualitative DWI scores (p = 0.42). Mean ADC was not different in those with and without histological inflammation (2077 vs. 1622 × 10 -6 mm 2 /s, p = 0.10) CONCLUSIONS: Qualitative grading of DWI signal has utility in defining the burden of CD activity. Quantitative ADC measurements have poor discriminatory ability for segmental disease activity.

Correlation between IL-17A/F, IL-23, IL-35 and IL-12/-23 (p40) levels in peripheral blood lymphocyte cultures and disease activity in Behcet's patients.

PubMed

Sonmez, Cemile; Yucel, Aysegul Atak; Yesil, Turan Hilmi; Kucuk, Hamit; Sezgin, Berna; Mercan, Ridvan; Yucel, Ahmet Eftal; Demirel, Gulderen Yanikkaya

2018-03-20

Behcet's disease is a chronic multisystemic disease with remissions and relapses. Several studies have shown that immune mechanisms play an important role in the development of the disease. In order to assess the association of disease activity with IL-17A/F, IL-23, IL-12/23 (p40) and IL-35 expression, we aimed to investigate production of these cytokines in peripheral blood mononuclear cells (PBMCs) from Behcet's patients and normal controls. Furthermore, we included Systemic Lupus Erythematosus (SLE) as disease control to evaluate the specificity of our data for immunopathogenesis of BD. Totally 15 active, 15 inactive Behcet's patients, 12 active and 12 inactive SLE patients and 12 healthy volunteers were enrolled in the study. Peripheral blood mononuclear cells were separated, lymphocyte cultures were performed and IL-17A/F, IL-12/23 p(40), IL-23, IL-35 cytokine levels were measured by ELISA in culture supernatants in the presence or absence of phytohemagglutinin (PHA) on time-dependent manner. IL-17 A/F levels increased parallel to IL-23 levels in Behcet's and SLE patients. Compared to healthy controls, IL-17 A/F levels were higher in active Behcet's and SLE patients; on the contrary, levels of IL-35 were lower. IL-17A/F, IL-12/23 (p40) and IL-23 levels were detectable most frequently in active Behcet's patients followed by active SLE patients. Our results indicate that IL-17 A/F, IL-23 and IL-12/23 (p40) may play role in the immunopathogenesis of BD so as Th17 and Th1 cell responses. Since IL-35 levels were lower in active Behcet's patients compared to inactive patients and healthy controls, there may be a plasticity between Th17 and Treg cells according to the state of disease activity.

To screen or not to screen? Celiac antibodies in liver diseases

PubMed Central

Narciso-Schiavon, Janaína Luz; Schiavon, Leonardo Lucca

2017-01-01

Celiac disease (CD) is a systemic immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals. The typical symptoms are anemia, diarrhea, fatigue, weight loss, and abdominal pain. CD has been reported in patients with primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis, aminotransferase elevations, nonalcoholic fatty liver disease, hepatitis B, hepatitis C, portal hypertension and liver cirrhosis. We evaluate recommendations for active screening for CD in patients with liver diseases, and the effect of a gluten-free diet in these different settings. Active screening for CD is recommended in patients with liver diseases, particularly in those with autoimmune disorders, steatosis in the absence of metabolic syndrome, noncirrhotic intrahepatic portal hypertension, cryptogenic cirrhosis, and in the context of liver transplantation. In hepatitis C, diagnosis of CD can be important as a relative contraindication to interferon use. Gluten-free diet ameliorates the symptoms associated with CD; however, the associated liver disease may improve, remain the same, or progress. PMID:28223722

Magnetic resonance enteroclysis in patients with Crohn's disease: fat saturated T2-weighted sequences for evaluation of inflammatory activity.

PubMed

Grieser, Christian; Denecke, Timm; Steffen, Ingo G; Werner, Scarlett; Kröncke, Thomas; Guckelberger, Olaf; Pape, Ulrich-Frank; Meier, Johannes; Thiel, Regina; Kivelitz, Dietmar; Sturm, Andreas; Hamm, Bernd; Röttgen, Rainer

2012-04-01

To evaluate fat saturated (fs) T2-weighted (w) fast relaxation fast spin echo (FRFSE)-sequences compared to the standard protocol with contrast agent for the evaluation of inflammatory activity in patients with Crohn's Disease (CD). Fourty-eight patients (male, 17; female, 33; mean age, 37 years) with suspicion of inflammatory activity in proven CD who underwent MR enteroclysis (MRE) at 1.5T (GE Healthcare) were retrospectively included. Two blinded radiologists analyzed MRE images for presence and extent of CD lesions and degree of local inflammation for fsT2-w FRFSE and contrast enhanced T1-w images (T2-activity; T1-activity; score, 1-4) in consensus. Furthermore, mural signal intensity (SI) ratios (T2-ratio; T1-ratio) were recorded. Patient based MRE findings were correlated with endoscopic (45 patients), surgical (6 patients), histopathological, and clinical data (CDAI) as a surrogate reference standard. In total, 24 of 48 eligible patients presented with acute inflammatory activity with 123 affected bowel segments. ROC analysis of the total inflammatory score presented an AUC of 0.93 (p<0.001) for T2-activity (T1-activity, AUC 0.63; p=0.019). ROC analysis revealed an AUC of 0.76 (p<0.001) for the T2-ratio (T1-ratio, AUC 0.51; p=0.93). General linear regression model revealed T2-activity (p=0.001) and age (p=0.024) as predictive factors of acute bowel inflammation. T2-w FRFSE-sequences can depict CD lesions and help to assess the inflammation activity, even with improved accuracy as compared to contrast-enhanced T1-w sequences. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Oxidative Stress in Aortas of Patients with Advanced Occlusive and Aneurysmal Diseases.

PubMed

Lucas, Márcio L; Carraro, Cristina C; Belló-Klein, Adriane; Kalil, Antônio N; Aerts, Newton R; Carvalho, Fabiano B; Fernandes, Marilda C; Zettler, Claudio G

2018-06-06

Aortoiliac occlusive disease (AOD) and abdominal aortic aneurysm (AAA) are very important cardiovascular diseases that present different aspects of pathophysiology; however, oxidative stress and inflammatory response seem be relevant in both of them. Our objective was to evaluate oxidative damage and degree of inflammatory infiltrate in aortas of patients surgically treated for AOD and AAA. Levels of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and myeloperoxidase (MPO) expression as well as nitrite levels and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in aortas of patients with AOD (n = 16) or AAA (n = 14), while the control group was formed by cadaveric organ donors (n = 10). We also analyzed the degree of inflammatory infiltrate in these aortas. There was an increase in ROS levels and NADPH oxidase activity in patients with AOD and AAA when compared with the control group, and the AOD group demonstrated higher ROS production and NADPH oxidase activity and also nitrite levels when compared with the AAA group (P < 0.001). On the other hand, an increase of SOD activity in the AOD group and CAT activity in the AAA group was observed. Inflammatory infiltrate and MPO expression were higher in the AOD group when compared with the control group (P < 0.05). Oxidative stress is relevant in both AOD and AAA, though AOD presented higher ROS levels and NADPH activity. Increased activities of antioxidant enzymes may be a compensatory phenomenon which occurs in aortas of patients with AOD and AAA. Perhaps, a relationship between oxidative stress and degree of inflammatory infiltrate may exist in the pathophysiology of AOD and AAA. Copyright © 2018 Elsevier Inc. All rights reserved.

A prospective functional MRI study for executive function in patients with systemic lupus erythematosus without neuropsychiatric symptoms.

PubMed

Mak, Anselm; Ren, Tao; Fu, Erin Hui-yun; Cheak, Alicia Ai-cia; Ho, Roger Chun-man

2012-06-01

To study the functional brain activation signals before and after sufficient disease control in patients with systemic lupus erythematosus (SLE) without clinical neuropsychiatric symptoms. Blood-oxygen-level-dependent signals during event-related functional magnetic resonance imaging brain were recorded, while 14 new-onset SLE patients and 14 demographically and intelligence quotient matched healthy controls performed the computer-based Wisconsin card sorting test for assessing executive function, which probes strategic planning and goal-directed task performance during feedback evaluation (FE) and response selection (RS), respectively. Composite beta maps were constructed by a general linear model to identify regions of cortical activation. Blood-oxygen-level-dependent functional magnetic resonance imaging signals were compared between (1) new-onset SLE patients and healthy controls and (2) SLE patients before and after sufficient control of their disease activity. During RS, SLE patients demonstrated significantly higher activation than healthy controls in both caudate bodies and Brodmann area (BA) 9 to enhance event anticipation, attention, and working memory, respectively, to compensate for the reduced activation during FE in BA6, 13, 24, and 32, which serve complex motor planning and decision-making, sensory integration, error detection, and conflict processing, respectively. Despite significant reduction of SLE activity, BA32 was activated during RS to compensate for reduced activation during FE in BA6, 9, 37, and 23/32, which serve motor planning, response inhibition and attention, color processing and word recognition, error detection, and conflict evaluation, respectively. Even without clinically overt neuropsychiatric symptoms, SLE patients recruited additional pathways to execute goal-directed tasks to compensate for their reduced strategic planning skill despite clinically sufficient disease control. Copyright © 2012 Elsevier Inc. All rights reserved.

Daily Physical Activity for Children and Youth: A Review and Synthesis of the Literature

ERIC Educational Resources Information Center

Bates, Heidi

2006-01-01

A Daily Physical Activity (DPA) Initiative was implemented in all schools in Alberta starting in September 2005. The expected outcome of the DPA Initiative is to increase the activity levels and healthy habits of students and, in part, address related issues such as chronic disease. As part of the first tier of the DPA Initiative evaluation study,…

The Public Health Service role in the disposal of chemical munitions.

PubMed Central

Brown, S T; Anderson, L W; Caldwell, G G

1985-01-01

Within the last decade, the Centers for Disease Control (CDC) has increasingly emphasized environmental public health activities. The Center for Environmental Health (CEH), one of nine major units of the CDC, was established as a focus for assessment and prevention of environmentally related diseases. Many new, legislatively mandated programs have been delegated to CEH. One such mandated responsibility in Public Laws 91-121 and 91-441 directs the Department of Health and Human Services or its designee to review the Department of Defense (DOD) plans to dispose of or to transport chemical warfare agents. The Chemical Munitions Demilitarization Program, CEH, reviews DOD plans and makes recommendations to ensure that hazards to public health and safety have been provided for in the plans. In addition, these CEH staffers periodically review approved activities at DOD facilities, assessing their monitoring and evaluation programs. CEH staffers also contact State and local health and environmental agencies to identify and evaluate any concerns of the agencies or the public relating to these activities. PMID:2991969

Telomerase activity in solid transitional cell carcinoma, bladder washings, and voided urine.

PubMed

Lance, R S; Aldous, W K; Blaser, J; Thrasher, J B

1998-03-04

Telomerase activity has been detected in a wide variety of human malignancies. It appears to be one of the fundamental ingredients necessary for cellular immortality. We sought to determine the incidence of telomerase activity in solid transitional cell carcinoma (TCC) specimens, benign urothelium, bladder washings, and voided urine from patients with TCC identified cystoscopically compared with controls. Telomerase activity was measured in 26 solid bladder cancers and 13 benign urothelial specimens using the telomere repeat amplification protocol (TRAP), a polymerase chain reaction (PCR) based assay. Telomerase activity was further measured in the centrifuged cellular material obtained from the bladder washings of 26 patients with TCC and 40 with benign urologic disease found to have a normal cystoscopy. All patients with hematuria were additionally evaluated with an upper tract radiographic examination and found to be free of malignancy. Voided urine was likewise evaluated in 11 patients with TCC, 12 with benign urologic diseases, and 56 asymptomatic control subjects. Telomerase activity was detected in 25 of 26 (96%) solid specimens, 21 of 26 (81%) bladder washings, and 6 of 11 (54%) voided urine specimens from patients with histologically confirmed TCC. In the control group, 2 of 13 (15%) benign urothelial specimens and 2 of 56 (4%) voided urine specimens from the asymptomatic volunteer group demonstrated telomerase activity. Of those with benign urologic disease, 16 of 40 (40%) bladder barbotage specimens and 6 of 12 (50%) voided urine specimens demonstrated telomerase activity. Sensitivity and specificity of telomerase as a marker for TCC were 81% and 60%, respectively, in the bladder washings group and 54% and 50%, respectively, in voided urine. These data indicate that activation of telomerase is frequent in solid TCC and appears to be a sensitive marker in bladder washings of patients with TCC. We noted an unexpectedly high false positive detection rate in patients with benign urologic diseases, especially those with symptomatic benign prostatic hyperplasia. An additional study of a larger number of both bladder cancer patients and those at risk is necessary to determine if telomerase activity could play a role as a diagnostic and/or surveillance marker of TCC. Published by Elsevier Science Inc.

[Review from the scientific paper about the main respiratory diseases in metallurgical workers].

PubMed

Apostoli, P; Catalani, S; Cortesi, I

2012-01-01

The review of main scientific investigations about the work related diseases in metallurgy shows that the most studied pathologies regards lung cancer and pneumoconiosis, other cancers and cardiovascular diseases. These evidences are not univocal and have been and are critically evaluated due to the complexity and articulated structure of metals production which makes it very difficult to compare the risks and diseases among the different metallurgical activities and, in the same activity, among the different job tasks. In addition, due to the technological and organizational evolution investigations, appear to be necessary to better define the specific hazards (for example metal species, PAH and PoPs mixtures) and to put into a correct relation these and pathologies diagnosed by health surveillance procedures or epidemiological surveys, surely different from those of past decades.

In vitro anticoagulant and antioxidant activities of Jatropha gossypiifolia L. (Euphorbiaceae) leaves aiming therapeutical applications.

PubMed

Félix-Silva, Juliana; Souza, Thiago; Camara, Rafael Barros Gomes; Cabral, Bárbara; Silva-Júnior, Arnóbio Antônio; Rebecchi, Ivanise Marina Moretti; Zucolotto, Silvana Maria; Rocha, Hugo Alexandre Oliveira; Fernandes-Pedrosa, Matheus de Freitas

2014-10-20

Jatropha gossypiifolia L. (Euphorbiaceae) is a medicinal plant largely used in folk medicine. Teas from the leaves are popularly used as an antithrombotic agent and the branches are frequently employed as a "thick blood" agent. Considering that the anticoagulant activity associated with antioxidant properties could be beneficial for various cardiovascular diseases, this study's aim is the evaluation of anticoagulant and antioxidant activities of J. gossypiifolia leaves, seeking new therapeutic purposes for this plant. The aqueous leaf crude extract (CE) was prepared by decoction and was fractionated by liquid-liquid partition with solvents of increasing polarity. The phytochemical analysis was performed by thin layer chromatography (TLC) and by the spectrophotometric quantification of sugars, proteins and phenolic compounds. The anticoagulant activity was evaluated by prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests. The capacity to act in the fibrinolytic system (fibrinolytic and fibrinogenolytic activities) was also assessed. The antioxidant activity was evaluated by total antioxidant capacity, reducing power, copper chelating activity, iron chelating activity, hydroxyl radical scavenging activity and superoxide radical scavenging assays. The potential toxicity was evaluated using hemolytic assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay on HEK-293 cells. CE showed significant anticoagulant activity in aPTT test, while no action was observed in PT test, suggesting a preferential action toward the intrinsic and/or common pathway of coagulation. No effect was observed in the fibrinolytic system. Using the aPTT test, it was observed that the residual aqueous (RA) fraction was the most active, being two times more active than CE. RA presented very significant antioxidant activity in all models tested comparable to or even higher than CE. Regarding the safety, CE and RA did not produce significant cytotoxicity in both tests employed. Phytochemical analysis revealed the presence of alkaloids, flavonoids, proteins, tannins, steroids and/or terpenoids and sugars. CE and RA possessed significant anticoagulant and antioxidant activity and absence of cytotoxic effect in vitro, thus showing the potential of the plant, especially RA fraction, as a new source of bioactive molecules for therapeutic purposes, with particular emphasis on the treatment of cardiovascular diseases.

Risk for latent and active tuberculosis in Germany.

PubMed

Herzmann, Christian; Sotgiu, Giovanni; Bellinger, Oswald; Diel, Roland; Gerdes, Silke; Goetsch, Udo; Heykes-Uden, Helga; Schaberg, Tom; Lange, Christoph

2017-06-01

Few individuals that are latently infected with M. tuberculosis latent tuberculosis infection(LTBI) progress to active disease. We investigated risk factors for LTBI and active pulmonary tuberculosis (PTB) in Germany. Healthy household contacts (HHCs), health care workers (HCWs) exposed to M. tuberculosis and PTB patients were recruited at 18 German centres. Interferon-γ release assay (IGRA) testing was performed. LTBI risk factors were evaluated by comparing IGRA-positive with IGRA-negative contacts. Risk factors for tuberculosis were evaluated by comparing PTB patients with HHCs. From 2008-2014, 603 HHCs, 295 HCWs and 856 PTBs were recruited. LTBI was found in 34.5% of HHCs and in 38.9% of HCWs. In HCWs, care for coughing patients (p = 0.02) and longstanding nursing occupation (p = 0.04) were associated with LTBI. In HHCs, predictors for LTBI were a diseased partner (odds ratio 4.39), sexual contact to a diseased partner and substance dependency (all p < 0.001). PTB was associated with male sex, low body weight (p < 0.0001), alcoholism (15.0 vs 5.9%; p < 0.0001), glucocorticoid therapy (7.2 vs 2.0%; p = 0.004) and diabetes (7.8 vs. 4.0%; p = 0.04). No contact developed active tuberculosis within 2 years follow-up. Positive IGRA responses are frequent among exposed HHCs and HCWs in Germany and are poor predictors for the development of active tuberculosis.

Influenza vaccination responses in human systemic lupus erythematosus: impact of clinical and demographic features

PubMed Central

Crowe, Sherry R.; Merrill, Joan T.; Vista, Evan S.; Dedeke, Amy B.; Thompson, David M.; Stewart, Scott; Guthridge, Joel M.; Niewold, Timothy B.; Franek, Beverly S.; Air, Gillian M.; Thompson, Linda F.; James, Judith A.

2011-01-01

Objective Vaccination against common pathogens, such as influenza, is recommended for SLE patients to decrease infections and improve health. However, most vaccination response reports are limited to evaluation of SLE patients with quiescent disease. This study focuses on understanding the clinical, serological, therapeutic, and demographic factors which influence the response to influenza vaccination in patients with a range of disease activities. Methods Blood specimens and disease activity information were collected from seventy-two SLE patients at baseline and 2, 6 and 12 weeks after influenza vaccination. Influenza-specific antibody responses were assessed for antibody concentration (Bmax), relative affinity (Ka), and hemagglutination inhibition (HAI). Using a cumulative score, the subjects were evenly divided into high and low responders. Autoantibody levels were evaluated at each time-point by immunofluorescence and standard ELISAs. Results Low responders to the vaccine were more likely to have hematologic criteria (p=0.009), exhibit more ACR criteria (p=0.05), and be on concurrent prednisone treatment (p=0.04). Interestingly, European American patients were more likely to be low responders than African Americans (p = 0.03). Following vaccination, low responders were more likely to experience disease flares (p=0.01) and to have increased ANA titers (p = 0.04). Baseline serum interferon alpha activity was significantly higher in patients that experienced a flare after vaccination compared to a matched group of patients that did not flare (p= 0.04). Conclusions Ancestral background, prednisone treatment, hematological criteria and evidence of increased disease flares were associated with low antibody responses to influenza vaccination in SLE patients. PMID:21598235

Putaminal dopamine depletion in de novo Parkinson's disease predicts future development of wearing-off.

PubMed

Chung, Su Jin; Lee, Yoonju; Oh, Jungsu S; Kim, Jae Seung; Lee, Phil Hyu; Sohn, Young H

2018-05-10

The present study aimed to investigate whether the level of presynaptic dopamine neuronal loss predicts future development of wearing-off in de novo Parkinson's disease. This retrospective cohort study included a total of 342 non-demented patients with de novo Parkinson's disease who underwent dopamine transporter positron emission tomography scans at their initial evaluation and received dopaminergic medications for 24 months or longer. Onset of wearing-off was determined based on patients' medical records at their outpatient clinic visits every 3-6 months. Predictive power of dopamine transporter activity in striatal subregions and other clinical factors for the development of wearing-off was evaluated by Cox proportional hazard models. During a median follow-up period of 50.2 ± 18.9 months, 69 patients (20.2%) developed wearing-off. Patients with wearing-off exhibited less dopamine transporter activity in the putamen, particularly the anterior and posterior putamens, compared to those without wearing-off. Multivariate Cox proportional hazard models revealed that dopamine transporter activities of the anterior (hazard ratio 0.556; p = 0.008) and whole putamens (hazard ratio 0.504; p = 0.025) were significant predictors of development of wearing-off. In addition, younger age at onset of Parkinson's disease, lower body weight, and a motor phenotype of postural instability/gait disturbance were also significant predictors for development of wearing-off. The present results provide in vivo evidence to support the hypothesis that presynaptic dopamine neuronal loss, particularly in the anterior putamen, leads to development of wearing-off in Parkinson's disease. Copyright © 2018. Published by Elsevier Ltd.

The Effects of Exercise on Cardiovascular Biomarkers: New Insights, Recent Data, and Applications.

PubMed

Che, Lin; Li, Dong

2017-01-01

The benefit of regular exercise or physical activity with appropriate intensity on improving cardiopulmonary function and endurance has long been accepted with less controversy. The challenge remains, however, quantitatively evaluate the effect of exercise on cardiovascular health due in part to the amount and intensity of exercise varies widely plus lack of effective, robust and efficient biomarker evaluation systems. Better evaluating the overall function of biomarker and validate biomarkers utility in cardiovascular health should improve the evidence regarding the benefit or the effect of exercise or physical activity on cardiovascular health, in turn increasing the efficiency of the biomarker on individuals with mild to moderate cardiovascular risk. In this review, beyond traditional cytokines, chemokines and inflammatory factors, we systemic reviewed the latest novel biomarkers in metabolomics, genomics, proteomics, and molecular imaging mainly focus on heart health, as well as cardiovascular diseases such as atherosclerosis and ischemic heart disease. Furthermore, we highlight the state-of-the-art biomarker developing techniques and its application in the field of heart health. Finally, we discuss the clinical relevance of physical activity and exercise on key biomarkers in molecular basis and practical considerations.

Association of large intergenic noncoding RNA expression with disease activity and organ damage in systemic lupus erythematosus.

PubMed

Wu, Yanfang; Zhang, Feifei; Ma, Jianyang; Zhang, Xiaoyan; Wu, Lingling; Qu, Bo; Xia, Shiwei; Chen, Shunle; Tang, Yuanjia; Shen, Nan

2015-05-21

Despite growing evidence that large intergenic noncoding RNAs (lincRNAs) can regulate gene expression and widely take part in normal physiological and disease conditions, our knowledge of systemic lupus erythematosus (SLE)-related lincRNAs remains limited. The aim of this study was to detect the levels of four lincRNAs (ENST00000500949: linc0949, ENST00000500597: linc0597, ENST00000501992: linc1992, and ENST00000523995: linc3995) involved in innate immunity in the peripheral blood mononuclear cells (PBMCs) of patients with SLE and correlate these lincRNA levels with disease activity, organ damage, clinical features and medical therapies. PBMCs were obtained from 102 patients with SLE, 54 patients with rheumatoid arthritis (RA) and 76 healthy donors. lincRNA expression levels were measured by real-time quantitative polymerase chain reaction. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores, and organ damage was evaluated with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. linc0949 and linc0597 were significantly decreased in patients with SLE compared with patients with RA and healthy control subjects. linc0949 was correlated with SLEDAI-2K score (r = -0.329, P = 0.0007), as well as with complement component C3 level (r = 0.348, P = 0.0003). The level of linc0949 was also reduced in patients with SLE who had the presence of cumulative organ damage. In addition, decreasing expression of linc0949 was associated with lupus nephritis. linc0949 expression significantly increased after treatment, whereas neither disease activity nor organ damage correlated with linc0597 expression. Our results provide novel empirical evidence that linc0949 could be a potential biomarker for diagnosis, disease activity and therapeutic response in SLE.

Long-term outcomes of treat-to-target strategy in established rheumatoid arthritis: a daily practice prospective cohort study.

PubMed

de Andrade, Nicole Pamplona Bueno; da Silva Chakr, Rafael Mendonça; Xavier, Ricardo Machado; Viecceli, Daniela; Correa, Ricardo Henrique Bilycz; de Oliveira Filho, Cilomar Martins; Brenol, Claiton Viegas

2017-06-01

To examine disease activity and physical function after implementation of treat-to-target (T2T) strategy in patients with established rheumatoid arthritis (RA) over a long-term period. Patients with RA were started on a T2T strategy in 2005 and followed through 2014. Patients were seen every 3-4 months until remission/low disease activity was achieved and every 6 months thereafter. Disease activity was measured by the DAS28 and CDAI, and physical function by the HAQ-DI. Results were presented as all observed data, without imputation for missing values. Changes in disease activity and physical function were evaluated by generalized estimating equations (GEE). Two hundred and twenty-nine patients were included, with a mean (SD) disease duration of 10.6 (7.4) years. Significant improvements were seen in both composite scores during the follow-up period, as demonstrated by DAS28 (β coefficient = 0.19; 95% CI = 0.16-0.21; p < 0.01) and by CDAI (β coefficient = 1.59; 95% CI = 1.84-1.34; p < 0.01). Physical function also improved, as demonstrated by HAQ-DI (β coefficient = 0.03; 95% CI = 0.02-0.04; p < 0.01). Biological therapy was associated with improvement in disease activity and in physical function. Leflunomide was only associated with improvement in physical function. Clinically meaningful reductions of DAS28, CDAI and HAQ-DI were observed in patients with established rheumatoid arthritis from 2005 to 2014. Implementation of new therapeutic options, in the scenario of T2T strategy, was associated with improvement in disease activity and physical function.

[Effect of disease severity on upper extremity muscle strength, exercise capacity, and activities of daily living in individuals with pulmonary arterial hypertension].

PubMed

Özcan Kahraman, Buse; Özsoy, İsmail; Acar, Serap; Özpelit, Ebru; Akdeniz, Bahri; Sevinç, Can; Savcı, Sema

2017-07-01

Pulmonary arterial hypertension (PAH) is a rare disease. Although muscle strength, exercise capacity, quality of life, and activities of daily living of patients with PAH are affected, it is not known how they are affected by disease severity. The purpose of the present study was to investigate effects of disease severity on upper extremity muscle strength, exercise capacity, and performance of activities of daily living in patients with PAH. Twenty-five patients with disease severity classified according to the New York Heart Association (NYHA) as functional class II (n=14) or class III (n=11) were included in the study. Upper-extremity exercise capacity and limitations in performing activities of daily living were assessed with 6-minute pegboard and ring test (6PBRT) and the Milliken activities of daily living scale (MAS), respectively. Shoulder flexion, elbow extension, elbow flexion muscle strength, and handgrip strength were measured with dynamometer. There were no significant differences in age, gender, body mass index, or mean pulmonary artery pressure between groups (p>0.05). The 6PBRT, MAS, and elbow flexion (right) and grip strength (right and left) results were significantly lower in NYHA III group than in NYHA II group (p=0.004, p=0.002, p=0.043, p=0.002 and p=0.003, respectively). There was no significant difference in shoulder flexion, elbow flexion (left), or elbow extension between groups (p>0.05). Results suggest that upper extremity exercise capacity, elbow flexion muscle strength (right), and handgrip strength decrease and that limitations in activities of daily living grow as disease severity increases in patients with PAH. When planning rehabilitation programs, disease severity should be considered and evaluations and treatments for the upper extremities should be included.

Reliability and Validity of an Internet-based Questionnaire Measuring Lifetime Physical Activity

PubMed Central

De Vera, Mary A.; Ratzlaff, Charles; Doerfling, Paul; Kopec, Jacek

2010-01-01

Lifetime exposure to physical activity is an important construct for evaluating associations between physical activity and disease outcomes, given the long induction periods in many chronic diseases. The authors' objective in this study was to evaluate the measurement properties of the Lifetime Physical Activity Questionnaire (L-PAQ), a novel Internet-based, self-administered instrument measuring lifetime physical activity, among Canadian men and women in 2005–2006. Reliability was examined using a test-retest study. Validity was examined in a 2-part study consisting of 1) comparisons with previously validated instruments measuring similar constructs, the Lifetime Total Physical Activity Questionnaire (LT-PAQ) and the Chasan-Taber Physical Activity Questionnaire (CT-PAQ), and 2) a priori hypothesis tests of constructs measured by the L-PAQ. The L-PAQ demonstrated good reliability, with intraclass correlation coefficients ranging from 0.67 (household activity) to 0.89 (sports/recreation). Comparison between the L-PAQ and the LT-PAQ resulted in Spearman correlation coefficients ranging from 0.41 (total activity) to 0.71 (household activity); comparison between the L-PAQ and the CT-PAQ yielded coefficients of 0.58 (sports/recreation), 0.56 (household activity), and 0.50 (total activity). L-PAQ validity was further supported by observed relations between the L-PAQ and sociodemographic variables, consistent with a priori hypotheses. Overall, the L-PAQ is a useful instrument for assessing multiple domains of lifetime physical activity with acceptable reliability and validity. PMID:20876666

Reliability and validity of an internet-based questionnaire measuring lifetime physical activity.

PubMed

De Vera, Mary A; Ratzlaff, Charles; Doerfling, Paul; Kopec, Jacek

2010-11-15

Lifetime exposure to physical activity is an important construct for evaluating associations between physical activity and disease outcomes, given the long induction periods in many chronic diseases. The authors' objective in this study was to evaluate the measurement properties of the Lifetime Physical Activity Questionnaire (L-PAQ), a novel Internet-based, self-administered instrument measuring lifetime physical activity, among Canadian men and women in 2005-2006. Reliability was examined using a test-retest study. Validity was examined in a 2-part study consisting of 1) comparisons with previously validated instruments measuring similar constructs, the Lifetime Total Physical Activity Questionnaire (LT-PAQ) and the Chasan-Taber Physical Activity Questionnaire (CT-PAQ), and 2) a priori hypothesis tests of constructs measured by the L-PAQ. The L-PAQ demonstrated good reliability, with intraclass correlation coefficients ranging from 0.67 (household activity) to 0.89 (sports/recreation). Comparison between the L-PAQ and the LT-PAQ resulted in Spearman correlation coefficients ranging from 0.41 (total activity) to 0.71 (household activity); comparison between the L-PAQ and the CT-PAQ yielded coefficients of 0.58 (sports/recreation), 0.56 (household activity), and 0.50 (total activity). L-PAQ validity was further supported by observed relations between the L-PAQ and sociodemographic variables, consistent with a priori hypotheses. Overall, the L-PAQ is a useful instrument for assessing multiple domains of lifetime physical activity with acceptable reliability and validity.

Evaluation of the Good Start Program: a healthy eating and physical activity intervention for Maori and Pacific Islander children living in Queensland, Australia.

PubMed

Mihrshahi, Seema; Vaughan, Lisa; Fa'avale, Nicola; De Silva Weliange, Shreenika; Manu-Sione, Inez; Schubert, Lisa

2017-01-13

Reducing the prevalence of obesity and chronic disease are important priorities. Maori and Pacific Islander communities living in Australia have higher rates of obesity and chronic disease than the wider Australian population. This study aims to assess the effectiveness of the Good Start program, which aims to improve knowledge, attitudes and practices related to healthy eating and physical activity amongst Maori and Pacific Islander communities living in Queensland. The intervention was delivered to children aged 6-19 years (N = 375) in schools by multicultural health workers. Class activities focused on one message each term related to healthy eating and physical activity using methods such as cooking sessions and cultural dance. The evaluation approach was a quantitative uncontrolled pre-post design. Data were collected each term pre- and post-intervention using a short questionnaire. There were significant increases in knowledge of correct servings of fruit and vegetables, knowledge of sugar and caffeine content of common sugar-sweetened drinks, recognition of the consequences of marketing and upsizing, and the importance of controlling portion size (all P < 0.05). There was also increases in knowledge of physical activity recommendations (P < 0.001), as well as the importance of physical activity for preventing heart disease (P < 0.001) and improving self-esteem (P < 0.001). In terms of attitudes, there were significant improvements in some attitudes to vegetables (P = 0.02), and sugar-sweetened drinks (P < 0.05). In terms of practices and behaviours, although the reported intake of vegetables increased significantly (P < 0.001), the proportion of children eating discretionary foods regularly did not change significantly, suggesting that modifying the program with an increased emphasis on reducing intake of junk food may be beneficial. The study has shown that the Good Start Program was effective in engaging children from Maori and Pacific Island backgrounds and in improving knowledge, and some attitudes and practices, related to healthy eating and physical activity. The evaluation contributes valuable information about components and impacts of this type of intervention, and considerations relevant to this population in order to successfully change behaviours and reduce the burden of chronic disease.

Peripheral blood cytokine and chemokine profiles in juvenile localized scleroderma

PubMed Central

Torok, Kathryn S.; Kurzinski, Katherine; Kelsey, Christina; Yabes, Jonathan; Magee, Kelsey; Vallejo, Abbe N.; Medsger, Thomas; Feghali-Bostwick, Carol A.

2015-01-01

Objective To evaluate peripheral blood T-helper (TH) cell associated cytokine and chemokine profiles in localized scleroderma (LS), and correlate them with clinical disease features, including disease activity parameters. Methods A 29-plex Luminex platform was used to analyze the humoral profile of plasma samples from 69 pediatric LS patients and 71 healthy pediatric controls. Cytokine/chemokine levels were compared between these two groups and within LS patients, focusing on validated clinical outcome measures of disease activity and damage in LS. Results Plasma levels of IP-10, MCP-1, IL-17a, IL-12p70, GM-CSF, PDGF-bb, IFN-α2, and IFN-γ were significantly higher in LS compared to healthy controls. Analysis within the LS group demonstrated IP-10, TNF-α and GM-CSF correlated with clinical measures of disease activity. Several cytokines/chemokines correlated with anti-histone antibody, while only a few correlated with positive ANA and single-stranded DNA antibody. Conclusion This is the first time that multiple cytokines and chemokines have been examined simultaneously LS. In general, a TH-1 (IFN-γ) and TH-17 (IL-17a) predominance was demonstrated in LS compared to healthy controls. There is also an IFN–γ signature with elevated IP-10, MCP-1 and IFN-γ, which has been previously demonstrated in systemic sclerosis, suggesting a shared pathophysiology. Within the LS patients, those with active disease demonstrated IP-10, TNF-α and GM-CSF, which may potentially serve as biomarkers of disease activity in the clinical setting. PMID:26254121

Temporal prolongation of decreased skin blood flow causes cold limbs in Parkinson's disease.

PubMed

Shindo, Kazumasa; Kobayashi, Fumikazu; Miwa, Michiaki; Nagasaka, Takamura; Takiyama, Yoshihisa; Shiozawa, Zenji

2013-03-01

To unravel the pathogenesis of cold limbs in Parkinson's disease, we evaluated cutaneous vasomotor neural function in 25 Parkinson's disease patients with or without cold limbs and 20 healthy controls. We measured resting skin sympathetic nerve activity, as well as reflex changes of skin blood flow and skin sympathetic nerve activity after electrical stimulation, with the parameters including skin sympathetic nerve activity frequency at rest, the amplitude of reflex bursts, the absolute decrease and percent reduction of blood flow, and the recovery time which was calculated as the interval from the start of blood flow reduction until the return to baseline cutaneous blood flow. The resting frequency of skin sympathetic nerve activity was significantly lower in patients with Parkinson's disease than in controls (p < 0.01). There were no significant differences between the patients and controls with respect to the amplitude of skin sympathetic nerve activity and the absolute decrease or percent reduction of blood flow volume. In the controls, the recovery time (9.4 ± 1.2), which was similar to Parkinson's disease patients without cold limbs (9.0 ± 0.7), while the recovery time ranged (15.7 ± 3.2) in Parkinson's disease patients with cold limbs. Recovery was significantly slower in these patients compared with the other groups (p < 0.05). It is possible that cold limbs might arise due to impaired circulation based on prolonged vasoconstriction by peripheral autonomic impairments, in addition to central autonomic dysfunction in Parkinson's disease.

Pathway activity inference for multiclass disease classification through a mathematical programming optimisation framework.

PubMed

Yang, Lingjian; Ainali, Chrysanthi; Tsoka, Sophia; Papageorgiou, Lazaros G

2014-12-05

Applying machine learning methods on microarray gene expression profiles for disease classification problems is a popular method to derive biomarkers, i.e. sets of genes that can predict disease state or outcome. Traditional approaches where expression of genes were treated independently suffer from low prediction accuracy and difficulty of biological interpretation. Current research efforts focus on integrating information on protein interactions through biochemical pathway datasets with expression profiles to propose pathway-based classifiers that can enhance disease diagnosis and prognosis. As most of the pathway activity inference methods in literature are either unsupervised or applied on two-class datasets, there is good scope to address such limitations by proposing novel methodologies. A supervised multiclass pathway activity inference method using optimisation techniques is reported. For each pathway expression dataset, patterns of its constituent genes are summarised into one composite feature, termed pathway activity, and a novel mathematical programming model is proposed to infer this feature as a weighted linear summation of expression of its constituent genes. Gene weights are determined by the optimisation model, in a way that the resulting pathway activity has the optimal discriminative power with regards to disease phenotypes. Classification is then performed on the resulting low-dimensional pathway activity profile. The model was evaluated through a variety of published gene expression profiles that cover different types of disease. We show that not only does it improve classification accuracy, but it can also perform well in multiclass disease datasets, a limitation of other approaches from the literature. Desirable features of the model include the ability to control the maximum number of genes that may participate in determining pathway activity, which may be pre-specified by the user. Overall, this work highlights the potential of building pathway-based multi-phenotype classifiers for accurate disease diagnosis and prognosis problems.

Analysis of disease activity and response to treatment in a large Spanish cohort of patients with systemic lupus erythematosus.

PubMed

Pego-Reigosa, J M; Rúa-Figueroa, Í; López-Longo, F J; Galindo-Izquierdo, M; Calvo-Alén, J; Olivé-Marqués, A; del Campo, V; García-Yébenes, M J; Loza-Santamaría, E; Blanco, R; Melero-González, R; Vela-Casasempere, P; Otón-Sánchez, T; Tomero-Muriel, E; Uriarte-Isacelaya, E; Fito-Manteca, M C; Freire-González, M; Narváez, J; Fernández-Nebro, A; Zea-Mendoza, A; Rosas, J; Carlos Rosas, J

2015-06-01

The objectives of this paper are to study the impact of disease activity in a large cohort of patients with systemic lupus erythematosus (SLE) and estimate the rate of response to therapies. We conducted a nationwide, retrospective, multicenter, cross-sectional cohort study of 3658 SLE patients. Data on demographics, disease characteristics: activity (SELENA-SLEDAI), damage, severity, hospitalizations and therapies were collected. Factors associated with refractory disease were identified by logistic regression. A total of 3658 patients (90% female; median SLE duration (interquartile range): 10.4 years (5.3-17.1)) were included. At the time of their last evaluation, 14.7% of the patients had moderate-severe SLE (SELENA-SLEDAI score ≥6). There were 1954 (53.4%) patients who were hospitalized for activity at least once over the course of the disease. At some stage, 84.6% and 78.8% of the patients received glucocorticoids and antimalarials, respectively, and 51.3% of the patients received at least one immunosuppressant. Owing to either toxicity or ineffectiveness, cyclophosphamide was withdrawn in 21.5% of the cases, mycophenolate mofetil in 24.9%, azathioprine in 40.2% and methotrexate in 46.8%. At some stage, 7.3% of the patients received at least one biologic. A total of 898 (24.5%) patients had refractory SLE at some stage. Renal, neuropsychiatric, vasculitic, hematological and musculoskeletal involvement, a younger age at diagnosis and male gender were associated with refractory disease. A significant percentage of patients have moderately-to-severely active SLE at some stage. Disease activity has a big impact in terms of need for treatment and cause of hospitalization. The effectiveness of the standard therapies for reducing disease activity is clearly insufficient. Some clinical features are associated with refractory SLE. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Calprotectin (S100A8/A9) and S100A12 are associated with measures of disease activity in a longitudinal study of patients with rheumatoid arthritis treated with infliximab.

PubMed

Nordal, H H; Brun, J G; Hordvik, M; Eidsheim, M; Jonsson, R; Halse, A-K

2016-07-01

The pro-inflammatory proteins calprotectin (a heterocomplex of S100A8/A9) and S100A12 have been associated with disease activity in rheumatoid arthritis (RA). The aim of this study was to compare their potential as biomarkers in a prospective study of RA patients starting with infliximab as their first biological disease-modifying anti-rheumatic drug (DMARD). Thirty-nine RA patients were examined and serum samples collected when starting with infliximab and after 3, 6, and 12 months. Calprotectin and S100A12 were analysed by enzyme-linked immunosorbent assays (ELISAs) and, together with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), measured at all time points. A disease activity score of 28 joints (DAS28) was calculated. Radiographs of the hands, wrists, and feet were taken at baseline and after 3 years, and assessed according to the modified Sharp/van der Heijde (SvH) score. Responsiveness was evaluated according to the European League of Associations for Rheumatology (EULAR) response criteria based on 28 joints. Both S100 proteins were significantly higher in seropositive than in seronegative patients (p = 0.01). Calprotectin correlated significantly with CRP (ρ = 0.51-0.75), ESR (ρ = 0.32-0.52), and DAS28 (ρ = 0.32-0.62). S100A12 correlated with calprotectin (ρ = 0.62-0.77) and CRP (ρ = 0.32-0.63). The S100 proteins, and especially calprotectin (ρ = 0.23-0.39), showed weak associations with radiographic progression, unlike CRP/ESR. None of the S100 proteins could predict responsiveness. Calprotectin showed the strongest correlation with measures of disease activity and may be better than S100A12 when evaluating disease activity in RA patients. More extensive studies are needed to further compare the predictive value of the S100 proteins relative to radiographic progression.

Vectra DA for the objective measurement of disease activity in patients with rheumatoid arthritis.

PubMed

Segurado, O G; Sasso, E H

2014-01-01

Quantitative and regular assessment of disease activity in rheumatoid arthritis (RA) is required to achieve treatment targets such as remission and to optimize clinical outcomes. To assess inflammation accurately, predict joint damage and monitor treatment response, a measure of disease activity in RA should reflect the pathological processes resulting in irreversible joint damage and functional disability. The Vectra DA blood test is an objective measure of disease activity for patients with RA. Vectra DA provides an accurate, reproducible score on a scale of 1 to 100 based on the concentrations of 12 biomarkers that reflect the pathophysiologic diversity of RA. The analytical validity, clinical validity, and clinical utility of Vectra DA have been evaluated for patients with RA in registries and prospective and retrospective clinical studies. As a biomarker-based instrument for assessing disease activity in RA, the Vectra DA test can help monitor therapeutic response to methotrexate and biologic agents and assess clinically challenging situations, such as when clinical measures are confounded by non-inflammatory pain from fibromyalgia. Vectra DA scores correlate with imaging of joint inflammation and are predictive for radiographic progression, with high Vectra DA scores being associated with more frequent and severe progression and low scores being predictive for non-progression. In summary, the Vectra DA score is an objective measure of RA disease activity that quantifies inflammatory status. By predicting risk for joint damage more effectively than conventional clinical and laboratory measures, it has the potential to complement these measures and optimise clinical decision making.

OVICIDAL EFFECT OF PIPERACEAE SPECIES ON Biomphalaria glabrata, Schistosoma mansoni HOST

PubMed Central

Rapado, Ludmila Nakamura; Lopes, Priscila Orechio de Moraes; Yamaguchi, Lydia Fumiko; Nakano, Eliana

2013-01-01

SUMMARY Schistosomiasis is a neglected disease with public health importance in tropical and subtropical regions. An alternative to the disease control is the use of molluscicides to eliminate or reduce the intermediate host snail population causing a reduction of transmission in endemic regions. In this study nine extracts from eight Piperaceae species were evaluated against Biomphalaria glabrata embryos at blastula stage. The extracts were evaluated in concentrations ranging from 100 to 10 mg/L. Piper crassinervium and Piper tuberculatum extracts were the most active (100% of mortality at 20 mg/L and 30 mg/L respectively). PMID:24213196

Information Technology and Lifestyle: A Systematic Evaluation of Internet and Mobile Interventions for Improving Diet, Physical Activity, Obesity, Tobacco, and Alcohol Use.

PubMed

Afshin, Ashkan; Babalola, Damilola; Mclean, Mireille; Yu, Zhi; Ma, Wenjie; Chen, Cheng-Yu; Arabi, Mandana; Mozaffarian, Dariush

2016-08-31

Novel interventions are needed to improve lifestyle and prevent noncommunicable diseases, the leading cause of death and disability globally. This study aimed to systematically review, synthesize, and grade scientific evidence on effectiveness of novel information and communication technology to reduce noncommunicable disease risk. We systematically searched PubMed for studies evaluating the effect of Internet, mobile phone, personal sensors, or stand-alone computer software on diet, physical activity, adiposity, tobacco, or alcohol use. We included all interventional and prospective observational studies conducted among generally healthy adults published between January 1990 and November 2013. American Heart Association criteria were used to evaluate and grade the strength of evidence. From 8654 abstracts, 224 relevant reports were identified. Internet and mobile interventions were most common. Internet interventions improved diet (N=20 studies) (Class IIa A), physical activity (N=33), adiposity (N=35), tobacco (N=22), and excess alcohol (N=47) (Class I A each). Mobile interventions improved physical activity (N=6) and adiposity (N=3) (Class I A each). Evidence limitations included relatively brief durations (generally <6 months, nearly always <1 year), heterogeneity in intervention content and intensity, and limited representation from middle/low-income countries. Internet and mobile interventions improve important lifestyle behaviors up to 1 year. This systematic review supports the need for long-term interventions to evaluate sustainability. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Item usage in a multidimensional computerized adaptive test (MCAT) measuring health-related quality of life.

PubMed

Paap, Muirne C S; Kroeze, Karel A; Terwee, Caroline B; van der Palen, Job; Veldkamp, Bernard P

2017-11-01

Examining item usage is an important step in evaluating the performance of a computerized adaptive test (CAT). We study item usage for a newly developed multidimensional CAT which draws items from three PROMIS domains, as well as a disease-specific one. The multidimensional item bank used in the current study contained 194 items from four domains: the PROMIS domains fatigue, physical function, and ability to participate in social roles and activities, and a disease-specific domain (the COPD-SIB). The item bank was calibrated using the multidimensional graded response model and data of 795 patients with chronic obstructive pulmonary disease. To evaluate the item usage rates of all individual items in our item bank, CAT simulations were performed on responses generated based on a multivariate uniform distribution. The outcome variables included active bank size and item overuse (usage rate larger than the expected item usage rate). For average θ-values, the overall active bank size was 9-10%; this number quickly increased as θ-values became more extreme. For values of -2 and +2, the overall active bank size equaled 39-40%. There was 78% overlap between overused items and active bank size for average θ-values. For more extreme θ-values, the overused items made up a much smaller part of the active bank size: here the overlap was only 35%. Our results strengthen the claim that relatively short item banks may suffice when using polytomous items (and no content constraints/exposure control mechanisms), especially when using MCAT.

A pragmatic randomised controlled trial of the Welsh National Exercise Referral Scheme: protocol for trial and integrated economic and process evaluation.

PubMed

Murphy, Simon; Raisanen, Larry; Moore, Graham; Edwards, Rhiannon Tudor; Linck, Pat; Williams, Nefyn; Ud Din, Nafees; Hale, Janine; Roberts, Chris; McNaish, Elaine; Moore, Laurence

2010-06-18

The benefits to health of a physically active lifestyle are well established and there is evidence that a sedentary lifestyle plays a significant role in the onset and progression of chronic disease. Despite a recognised need for effective public health interventions encouraging sedentary people with a medical condition to become more active, there are few rigorous evaluations of their effectiveness. Following NICE guidance, the Welsh national exercise referral scheme was implemented within the context of a pragmatic randomised controlled trial. The randomised controlled trial, with nested economic and process evaluations, recruited 2,104 inactive men and women aged 16+ with coronary heart disease (CHD) risk factors and/or mild to moderate depression, anxiety or stress. Participants were recruited from 12 local health boards in Wales and referred directly by health professionals working in a range of health care settings. Consenting participants were randomised to either a 16 week tailored exercise programme run by qualified exercise professionals at community sports centres (intervention), or received an information booklet on physical activity (control). A range of validated measures assessing physical activity, mental health, psycho-social processes and health economics were administered at 6 and 12 months, with the primary 12 month outcome measure being 7 day Physical Activity Recall. The process evaluation explored factors determining the effectiveness or otherwise of the scheme, whilst the economic evaluation determined the relative cost-effectiveness of the scheme in terms of public spending. Evaluation of such a large scale national public health intervention presents methodological challenges in terms of trial design and implementation. This study was facilitated by early collaboration with social research and policy colleagues to develop a rigorous design which included an innovative approach to patient referral and trial recruitment, a comprehensive process evaluation examining intervention delivery and an integrated economic evaluation. This will allow a unique insight into the feasibility, effectiveness and cost effectiveness of a national exercise referral scheme for participants with CHD risk factors or mild to moderate anxiety, depression, or stress and provides a potential model for future policy evaluations. Current Controlled Trials ISRCTN47680448.

[Improving prevention activities of infectious diseases during preparation and holding of the XXII Olympic Winter Games and XI Paralympic Winter Games 2014 in Sochi].

PubMed

Onishchenko, G G; Bragina, I V; Ezhlova, E B; Demina, Iu V; Grechanaia, T V; Nikolaevich, P N; Balaeva, M I; Tesheva, S Ch; Biriukov, V A; Kulichenko, A N; Vasilenko, N F; Maletskaia, O V; Manin, E A; Orobeĭ, V G

2015-01-01

The article presents data on the implementation of a set of preventive activities to ensure sanitation and epidemiological welfare during the XXII Olympic Winter Games and XI Paralympic Winter Games 2014 in Sochi. The importance of monitoring and evaluation of epidemiological risk, as the basis of formation of preventive measures is noticed. The questions of specific, and nonspecific prevention of infectious diseases, especially the work done during the pre-Olympic period are considered. The importance of specifically developed regulatory basis, and health education are emphasized. The conclusion about the effectiveness of the measures taken, which led to a significant reduction of infectious diseases in the region is made.

Nutritional factors in the biochemical pathology of Corynebacterial kidney disease in the coho salmon (Oncorhynchus kisutch)

USGS Publications Warehouse

Wedemeyer, Gary A.; Ross, A.J.

1973-01-01

The influence of diet ingredient on the morbidity and biochemical pathogenesis of corynebacterial kidney disease was investigated using juvenile coho salmon (Oncorhynchus kisutch) fed the Abernathy dry ration made up with either corn gluten or cottonseed meal (isoprotein, isocaloric substitution). Evaluation of incidence of infection, pituitary activation and aspects of carbohydrate metabolism, acid-base balance, renal function, and hematopoietic activity showed that the actual disease incidence was about the same for both diets but the nonspecific stress of infection was more severe in fish fed the corn gluten.Discriminant function calculations combining four physiological parameters gave a probability of 0.86 for successfully diagnosing infected fish on the basis of these blood chemistry tests.

Perianal Crohn's disease - association with significant inflammatory activity in proximal small bowel segments.

PubMed

Xavier, Sofia; Cúrdia Gonçalves, Tiago; Dias de Castro, Francisca; Magalhães, Joana; Rosa, Bruno; Moreira, Maria João; Cotter, José

2018-04-01

Perianal Crohn's disease (CD) prevalence varies according to the disease location, being particularly frequent in patients with colonic involvement. We aimed to evaluate small bowel involvement and compare small bowel capsule endoscopy findings and inflammatory activity between patients with and without perianal disease. Retrospective single-center study including 71 patients - all patients with perianal CD (17 patients) who performed a small bowel capsule endoscopy were included, and non-perianal CD patients were randomly selected (54 patients). Clinical and analytical variables at diagnosis were reviewed. Statistical analysis was performed with SPSS v21.0 and a two-tailed p value <.05 was defined as indicating statistical significance. Patients had a median age of 30 ± 16 years with 52.1% females. Perianal disease was present in 23.9%. Patients with perianal disease had significantly more relevant findings (94.1% vs 66.6%, p = .03) and erosions (70.6% vs 42.6%, p = .04), however, no differences were found between the two groups regarding ulcer, villous edema and stenosis detection. Overall, patients with perianal disease had more frequently significant small bowel inflammatory activity, defined as a Lewis Score ≥135 (94.1% vs 64.8%, p = .03), and higher Lewis scores in the first and second tertiles (450 ± 1129 vs 0 ± 169, p = .02 and 675 ± 1941 vs 0 ± 478, p = .04, respectively). No differences were found between the two groups regarding third tertile inflammatory activity assessed with the Lewis Score. Patients with perianal CD have significantly higher inflammatory activity in the small bowel, particularly in proximal small bowel segments, when compared with patients without perianal disease.

Cross-cultural adaptation and validation of the Behcet’s Disease Current Activity Form in Korea

PubMed Central

Choi, Hyo Jin; Seo, Mi Ryoung; Ryu, Hee Jung; Baek, Han Joo

2015-01-01

Background/Aims: This study was undertaken to perform a cross-cultural adaptation of the Behcet’s Disease Current Activity Form (BDCAF, version 2006) questionnaire to the Korean language and to evaluate its reliability and validity in a population of Korean patients with Behcet’s disease (BD). Methods: A cross-cultural study was conducted among patients with BD who attended our rheumatology clinic between November 2012 and March 2013. There were 11 males and 35 females in the group. The mean age of the participants was 48.5 years and the mean disease duration was 6.4 years. The first BDCAF questionnaire was completed on arrival and the second assessment was performed 20 minutes later by a different physician. The test-retest reliability was analyzed by computing κ statistics. Kappa scores of > 0.6 indicated a good agreement. To assess the validity, we compared the total BDCAF score with the patient’s/clinician’s perception of disease activity and the Korean version of the Behcet’s Disease Quality of Life (BDQOL). Results: For the test-retest reliability, good agreements were achieved on items such as headache, oral/genital ulceration, erythema, skin pustules, arthralgia, nausea/vomiting/abdominal pain, and diarrhea with altered/frank blood per rectum. Moderate agreement was observed for eye and nervous system involvement. We achieved a fair agreement for arthritis and major vessel involvement. Significant correlations were obtained between the total BDCAF score with the BDQOL and the patient’s/clinician’s perception of disease activity p < 0.05). Conclusions: The Korean version of the BDCAF is a reliable and valid instrument for measuring current disease activity in Korean BD patients. PMID:26354066

Neuroprotective effects of the antiparkinson drug Mucuna pruriens.

PubMed

Manyam, Bala V; Dhanasekaran, Muralikrishnan; Hare, Theodore A

2004-09-01

Mucuna pruriens possesses significantly higher antiparkinson activity compared with levodopa in the 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease. The present study evaluated the neurorestorative effect of Mucuna pruriens cotyledon powder on the nigrostriatal tract of 6-OHDA lesioned rats. Mucuna pruriens cotyledon powder significantly increased the brain mitochondrial complex-I activity but did not affect the total monoamine oxidase activity (in vitro). Unlike synthetic levodopa treatment, Mucuna pruriens cotyledon powder treatment significantly restored the endogenous levodopa, dopamine, norepinephrine and serotonin content in the substantia nigra. Nicotine adenine dinucleotide (NADH) and coenzyme Q-10, that are shown to have a therapeutic benefit in Parkinson's disease, were present in the Mucuna pruriens cotyledon powder. Earlier studies showed that Mucuna pruriens treatment controls the symptoms of Parkinson's disease. This additional finding of a neurorestorative benefit by Mucuna pruriens cotyledon powder on the degenerating dopaminergic neurons in the substantia nigra may be due to increased complex-I activity and the presence of NADH and coenzyme Q-10. Copyright (c) 2004 John Wiley & Sons, Ltd.

Selective reactivation of human herpesvirus 6 in patients with autoimmune connective tissue diseases.

PubMed

Broccolo, Francesco; Drago, Francesco; Cassina, Giulia; Fava, Andrea; Fusetti, Lisa; Matteoli, Barbara; Ceccherini-Nelli, Luca; Sabbadini, Maria Grazia; Lusso, Paolo; Parodi, Aurora; Malnati, Mauro S

2013-11-01

Viral infections have been associated with autoimmune connective tissue diseases. To evaluate whether active infection by Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus (HHV)-6, -7, -8, as well as parvovirus B19 (B19V) occur in patients with autoimmune connective tissue diseases, viral DNA loads were assessed in paired samples of serum and peripheral blood mononuclear cells (PBMCs) of 115 patients affected by different disorders, including systemic sclerosis, systemic, and discoid lupus erythematosus, rheumatoid arthritis, and dermatomyositis. Two additional groups, patients affected by inflammatory diseases (n=51) and healthy subjects (n=58) were studied as controls. The titers of anti-HHV-6 and anti-EBV antibodies were also evaluated. Cell-free HHV-6 serum viremia was detected in a significantly higher proportion of connective tissue diseases patients compared to controls (P<0.0002); a significant association between HHV-6 reactivation and the active disease state was found only for lupus erythematosus (P=0.021). By contrast, the rate of cell-free EBV viremia was similar in patients and controls groups. Cell-free CMV, HHV-8, and B19V viremia was not detected in any subject. Anti-HHV-6 and anti-EBV early antigen IgG titers were both significantly higher in autoimmune diseases patients as compared to healthy controls, although they were not associated with the presence of viremia. EBV, HHV-6, -7 prevalence and viral load in PBMCs of patients with connective tissue diseases and controls were similar. These data suggest that HHV-6 may act as a pathogenic factor predisposing patients to the development of autoimmune connective tissue diseases or, conversely, that these disorders may predispose patients to HHV-6 reactivation. © 2013 Wiley Periodicals, Inc.

Associations between plasma fatty acids, desaturase and elongase, and insulin resistance in children

USDA-ARS?s Scientific Manuscript database

Background and Objectives - Fatty acid profiles, desaturase (SCD-16, SCD018, D5D, D6D) and elongase (ELOVL6) enzyme activity have been associated with adiposity and metabolic disease. While this has been studied in adults, few studies have evaluated children. The objective of this study was to evalu...

Economic evaluation of an area-wide integrated pest management program to control the Asian tiger mosquito in New Jersey

USDA-ARS?s Scientific Manuscript database

Aedes albopictus is the most invasive mosquito in the world, an important disease vector, and a biting nuisance that limits outdoor activities. Area-wide integrated pest management (AW-IPM) is the recommended control strategy. We conducted an economic evaluation of the AW-IPM project in Mercer and ...

HDL Function in Rheumatoid Arthritis

PubMed Central

Ormseth, Michelle J; Stein, C. Michael

2015-01-01

Purpose of review Patients with rheumatoid arthritis (RA) have accelerated atherosclerosis despite the appearance of having a less atherogenic lipid profile; however, lipoprotein function rather than concentration may be a better indicator of atherosclerotic risk. The purpose of this review is to summarize recent findings concerning HDL function in patients with RA. Recent findings Two major activities of HDL, its antioxidant and cholesterol efflux functions have been examined in RA. HDL antioxidant capacity is inversely associated with inflammation and RA disease activity; however, there is no clear consensus if antioxidant capacity is altered significantly in RA compared to control subjects. Moreover, despite numerous studies there is no consensus whether HDL cholesterol efflux capacity is significantly altered in RA compared to control subjects or influenced by inflammation or disease activity. Summary Additional studies will be valuable to consolidate existing data and find consensus. Moreover, studies evaluating the impact of various HDL functions on cardiovascular disease in RA are needed. PMID:26709471

Prevalence of hypothyroidism in rheumatoid arthritis and its correlation with disease activity.

PubMed

Joshi, Prakash; Agarwal, Abhishek; Vyas, Sony; Kumar, Ravindra

2017-01-01

To analyse the prevalence of hypothyroidism in rheumatoid arthritis (RA) patients and to elucidate its correlation with disease activity. A total of 52 RA patients were enrolled in this study. All patients were assessed fully clinically and underwent routine laboratory investigation including thyroid function testing. Hypothyroidism (defined as having a TSH level >4.20 μIU/mL) was observed in 20/52 (38.4%). Erythrocyte sedimentation rates (ESR) were found significantly elevated in patients with hypothyroidism compared to those without (36.3 ± 24.2 vs. 24.6 ± 9.0 mm/h). Disease activity parameters such as DAS-28-ESR, tender joint count; VAS scores were also significantly higher in the former. A significant correlation with serum TSH levels was observed with ESR and DAS-28-ESR. Thyroid function test should be included in clinical evaluation of RA patients. © The Author(s) 2016.

Patients with Ankylosing Spondylitis and Low Disease Activity because of Anti-TNF-Alpha Therapy Have Higher TRAIL Levels Than Controls: A Potential Compensatory Effect

PubMed Central

López-Mejías, Raquel; Rueda-Gotor, Javier; Miranda-Filloy, José A.; Ubilla, Begoña; Carnero-López, Beatriz; Palmou-Fontana, Natalia; Gómez-Acebo, Inés; Blanco, Ricardo; Pina, Trinitario; Ochoa, Rodrigo; González-Juanatey, Carlos; González-Gay, Miguel A.

2014-01-01

Objective. TRAIL is a potential biomarker of cardiovascular (CV) disease. Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with metabolic syndrome (MeS) and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-α antagonist infliximab therapy and if infliximab infusion modified TRAIL levels. Methods. We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNF-α therapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-α infusion were analyzed. Results. TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-α infusion did not change TRAIL levels after 120′. Conclusion. Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients. PMID:24976690

STAT3 Inhibitory Activity of Structurally Simplified Withaferin A Analogues.

PubMed

Tahara, Teruyuki; Streit, Ursula; Pelish, Henry E; Shair, Matthew D

2017-04-07

Signal transducer and activator of transcription 3 (STAT3) is a component of the JAK/STAT pathway. Therapeutic inhibition of STAT3 has been of high interest, as its aberrant activation has been linked to cancer, inflammation, and other human diseases. The withanolide family natural product withaferin A (1) inhibits STAT3 activation. We designed, synthesized, and evaluated simplified withanolide analogues SLW1 (3) and SLW2 (4), and found that SLW1 retained the STAT3 inhibitory activity of withaferin A.

Quality of life in people with Parkinson's disease: the relevance of social relationships and communication.

PubMed

Takahashi, Kayoko; Kamide, Naoto; Suzuki, Makoto; Fukuda, Michinari

2016-01-01

[Purpose] Maintaining high quality of life is crucial for the rehabilitation of patients with Parkinson's disease. The quality of life scales currently in use do not assess all quality of life domains or their importance for each individual. Therefore, a new quality of life measure, the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting, was used to investigate quality of life in people with Parkinson's disease. [Subjects and Methods] Fifteen people with idiopathic Parkinson's disaese (average age = 80.0 years, standard deviation = 10.3 years, Hoehn & Yahr stages 1-4) were interviewed using the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting. Its quality of life constructs were tested by comparing them against disease-specific quality of life (39-items Parkinson's Disease Questionnaire), motor functioning (Unified Parkinson's Disease Rating Scale Part III), and activities of daily living (Barthel Index). [Results] Social connections such as "family" and "friends" were revealed as important constructs of life satisfaction. The Schedule for the Evaluation of Individual Quality of Life-Direct Weighting was not significantly correlated with the 39-items Parkinson's Disease Questionnaire, Unified Parkinson's Disease Rating Scale Part III, or Barthel Index but was significantly correlated with the "communication" dimension of the 39-items Parkinson's Disease Questionnaire. [Conclusion] The Schedule for the Evaluation of Individual Quality of Life-Direct Weighting detected various domains of quality of life, especially social relationships with family and friends. "Being heard" was also revealed as an essential component of life satisfaction, as it provides patients with a feeling of acceptance and assurance, possibly resulting in better quality of life.

Vascular endothelial growth factor in systemic lupus erythematosus - correlations with disease activity and nailfold capillaroscopy changes.

PubMed

Bărbulescu, Andreea Lili; Vreju, Ananu Florentin; Bugă, Ana Maria; Sandu, Raluca Elena; Criveanu, Cristina; Tudoraşcu, Diana Rodica; Gheonea, Ioana Andreea; Ciurea, Paulina Lucia

2015-01-01

Our study aimed to quantify serum VEGF (vascular endothelial growth factor) and its inter-relation with the severity of microvascular damage, assessed by nailfold capillaroscopy (NC), and to establish the possible relationship with disease activity score. We included 18 patients, diagnosed with systemic lupus erythematosus (SLE) and 17 gender and age-matched control subjects. For determining serum VEGF, we used a Human VEGF Assay kit-IBL. NC was performed, according to the standard method, using a video-capillaroscope Videocap 3.0, DS Medica, by the same examiner, blinded to clinical and laboratory data. Serum VEGF registered a mean value of 68.99±71.06 pg/mL for SLE patients and 31.84±11.74 pg/mL for controls, differences statistically significant; depending on disease activity, we found a mean value of 60.11±57.74 pg/mL, for patients with moderate disease activity vs. 30.96±11.51 pg/mL for the ones with a low activity (p=0.014). We found a moderately positive correlation, statistically significant (p=0.015), between serum level of VEGF and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Performing NC, we found changes in 88.88% of the patients; the most frequent were increased tortuosity, dilated capillaries, an increased length and a prominent subpapillary plexus. The presence of nailfold capillaroscopy changes and serum level of VEGF, correlated moderately, positive. Since serum levels of VEGF are higher in SLE patients, compared to controls, significantly different according to disease activity degree, and directly inter-related to abnormal NC patterns and a more active disease, we can include these accessible parameters in the routine evaluation, in order to better quantify the systemic damage, individualize the treatment, improve the outcome and life quality for these patients.

Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis

PubMed Central

Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

2016-01-01

Abstract Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality. PMID:27100422

Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis.

PubMed

Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

2016-04-01

Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality.

Success and Challenges of a Community Healthy Lifestyles Intervention in Merseyside (UK) to Target Families at Risk from Coronary Heart Disease

ERIC Educational Resources Information Center

Peerbhoy, D.; Majumdar, A. J.; Wightman, N. A.; Brand, V. L.

2008-01-01

Objective: To document the lifestyle health impacts (activity, diet and physiological), along with the operational success and challenges, of a programme for families presenting one or more coronary heart disease (CHD) risk factor. Design: Data are based on a wider evaluation of a government-funded community initiative conducted in a deprived area…

Short health scale: A valid measure of health-related quality of life in Korean-speaking patients with inflammatory bowel disease

PubMed Central

Park, Soo-Kyung; Ko, Bong Min; Goong, Hyeon Jeong; Seo, Jeong Yeon; Lee, Sang Hyuk; Baek, Hae Lim; Lee, Moon Sung; Park, Dong Il

2017-01-01

AIM To evaluate the short health scale (SHS), a new, simple, four-part visual analogue scale questionnaire that is designed to assess the impact of inflammatory bowel disease (IBD) on health-related quality of life (HRQOL), in Korean-speaking patients with IBD. METHODS The SHS was completed by 256 patients with Crohn’s disease (CD) and ulcerative colitis (UC). Individual SHS items were correlated with inflammatory bowel disease questionnaire (IBDQ) dimensions and with disease activity to assess validity. Test-retest reliability, responsiveness and patient or disease characteristics with probable association with high SHS scores were analyzed. RESULTS Of 256 patients with IBD, 139 (54.3%) had UC and 117 (45.7%) had CD. The correlation coefficients between SHS questions about “symptom burden”, “activities of daily living”, and “disease-related worry” and their corresponding dimensions in the IBDQ ranged from 0.62 to 0.71, compared with correlation coefficients ranging from -0.45 to -0.61 for their non-corresponding dimensions. There was a stepwise increase in SHS scores, with increasing disease activity in both CD and UC (all P values < 0.001). Reliability was confirmed with test-retest correlations ranging from 0.68 to 0.90 (all P values < 0.001). Responsiveness was confirmed with the patients who remained in remission. Their SHS scores remained unchanged, except for the SHS dimension “disease-related worry”. In the multivariate analysis, female sex was associated with worse “general well-being” (OR = 2.28, 95%CI: 1.02-5.08) along with worse disease activity. CONCLUSION The SHS is a valid and reliable measure of HRQOL in Korean-speaking patients with IBD. PMID:28596689

Short health scale: A valid measure of health-related quality of life in Korean-speaking patients with inflammatory bowel disease.

PubMed

Park, Soo-Kyung; Ko, Bong Min; Goong, Hyeon Jeong; Seo, Jeong Yeon; Lee, Sang Hyuk; Baek, Hae Lim; Lee, Moon Sung; Park, Dong Il

2017-05-21

To evaluate the short health scale (SHS), a new, simple, four-part visual analogue scale questionnaire that is designed to assess the impact of inflammatory bowel disease (IBD) on health-related quality of life (HRQOL), in Korean-speaking patients with IBD. The SHS was completed by 256 patients with Crohn's disease (CD) and ulcerative colitis (UC). Individual SHS items were correlated with inflammatory bowel disease questionnaire (IBDQ) dimensions and with disease activity to assess validity. Test-retest reliability, responsiveness and patient or disease characteristics with probable association with high SHS scores were analyzed. Of 256 patients with IBD, 139 (54.3%) had UC and 117 (45.7%) had CD. The correlation coefficients between SHS questions about "symptom burden", "activities of daily living", and "disease-related worry" and their corresponding dimensions in the IBDQ ranged from 0.62 to 0.71, compared with correlation coefficients ranging from -0.45 to -0.61 for their non-corresponding dimensions. There was a stepwise increase in SHS scores, with increasing disease activity in both CD and UC (all P values < 0.001). Reliability was confirmed with test-retest correlations ranging from 0.68 to 0.90 (all P values < 0.001). Responsiveness was confirmed with the patients who remained in remission. Their SHS scores remained unchanged, except for the SHS dimension "disease-related worry". In the multivariate analysis, female sex was associated with worse "general well-being" (OR = 2.28, 95%CI: 1.02-5.08) along with worse disease activity. The SHS is a valid and reliable measure of HRQOL in Korean-speaking patients with IBD.

Autologous Hematopoetic Stem Cell Transplantation for Refractory Crohn Disease: A Randomized Clinical Trial.

PubMed

Hawkey, Christopher J; Allez, Matthieu; Clark, Miranda M; Labopin, Myriam; Lindsay, James O; Ricart, Elena; Rogler, Gerhard; Rovira, Montserrat; Satsangi, Jack; Danese, Silvio; Russell, Nigel; Gribben, John; Johnson, Peter; Larghero, Jerome; Thieblemont, Catherine; Ardizzone, Sandro; Dierickx, Daan; Ibatici, Adalberto; Littlewood, Timothy; Onida, Francesco; Schanz, Urs; Vermeire, Severine; Colombel, Jean-Frederic; Jouet, Jean-Paul; Clark, Elizabeth; Saccardi, Riccardo; Tyndall, Alan; Travis, Simon; Farge, Dominique

2015-12-15

Case reports and series suggest hematopoietic stem cell transplantation (HSCT) may benefit some patients with Crohn disease. To evaluate the effect of autologous HSCT on refractory Crohn disease. Parallel-group randomized clinical trial conducted in 11 European transplant units from July 2007 to September 2011, with follow-up through March 2013. Patients were aged 18 to 50 years with impaired quality of life from refractory Crohn disease not amenable to surgery despite treatment with 3 or more immunosuppressive or biologic agents and corticosteroids. All patients underwent stem cell mobilization before 1:1 randomization to immunoablation and HSCT (n = 23) or control treatment (HSCT deferred for 1 year [n = 22]). All were given standard Crohn disease treatment as needed. Sustained disease remission at 1 year, a composite primary end point comprising clinical remission (Crohn Disease Activity Index (CDAI) <150 [range, 0-600]), no use of corticosteroids or immunosuppressive or biologic drugs for at least the last 3 months, and no endoscopic or radiological evidence of active (erosive) disease anywhere in the gastrointestinal (GI) tract. Secondary outcomes were individual components of the primary composite outcome and other measures of disease activity, laboratory results, quality of life and functional status, and GI tract imaging. Twenty-three patients underwent HSCT and 22 received standard Crohn disease treatment (controls). Sustained disease remission was achieved in 2 patients undergoing HSCT (8.7%) vs 1 control patient (4.5%) (absolute difference, 4.2% [95% CI, -14.2% to 22.6%]; P = .60). Fourteen patients undergoing HSCT (61%) vs 5 control patients (23%) had discontinued immunosuppressive or biologic agents or corticosteroids for at least 3 months (difference, 38.1% [95% CI, 9.3% to 59.3%]; P = .01). Ten vs 2 patients had a CDAI less than 150 (remission) at the final evaluation, 8 (34.8%) vs 2 (9.1%) for 3 or more months (difference, 25.7% [95% CI, 1.1% to 47.1%]; P = .052). Eight (34.8%) vs 2 (9.1%) patients were adjudicated free of active disease on endoscopy and radiology at final assessment (difference, 25.7% [95% CI, 1.1% to 47.1%]; P = .054). There were 76 serious adverse events in patients undergoing HSCT vs 38 in controls. One patient undergoing HSCT died. Among adult patients with refractory Crohn disease not amenable to surgery who had impaired quality of life, HSCT, compared with conventional therapy, did not result in a statistically significant improvement in sustained disease remission at 1 year and was associated with significant toxicity. These findings do not support the widespread use of HSCT for patients with refractory Crohn disease. clinicaltrials.gov Identifier: NCT00297193.

Angiotensin-converting enzyme-inhibitory activity in protein hydrolysates from normal and anthracnose disease-damaged Phaseolus vulgaris seeds.

PubMed

Hernández-Álvarez, Alan Javier; Carrasco-Castilla, Janet; Dávila-Ortiz, Gloria; Alaiz, Manuel; Girón-Calle, Julio; Vioque-Peña, Javier; Jacinto-Hernández, Carmen; Jiménez-Martínez, Cristian

2013-03-15

Bean seeds are an inexpensive source of protein. Anthracnose disease caused by the fungus Colletotrichum lindemuthianum results in serious losses in common bean (Phaseolus vulgaris L.) crops worldwide, affecting any above-ground plant part, and protein dysfunction, inducing the synthesis of proteins that allow plants to improve their stress tolerance. The aim of this study was to evaluate the use of beans damaged by anthracnose disease as a source of peptides with angiotensin-converting enzyme (ACE-I)-inhibitory activity. Protein concentrates from beans spoiled by anthracnose disease and from regular beans as controls were prepared by alkaline extraction and precipitation at isolelectric pH and hydrolysed using Alcalase 2.4 L. The hydrolysates from spoiled beans had ACE-I-inhibitory activity (IC(50) 0.0191 mg protein mL(-1)) and were very similar to those from control beans in terms of ACE-I inhibition, peptide electrophoretic profile and kinetics of hydrolysis. Thus preparation of hydrolysates using beans affected by anthracnose disease would allow for revalorisation of this otherwise wasted product. The present results suggest the use of spoiled bean seeds, e.g. anthracnose-damaged beans, as an alternative for the isolation of ACE-I-inhibitory peptides to be further introduced as active ingredients in functional foods. © 2012 Society of Chemical Industry.

Cardiac health: primary prevention of heart disease in women.

PubMed

Turk, Melanie Warziski; Tuite, Patricia K; Burke, Lora E

2009-09-01

Heart disease is the number one cause of death among women. Although 450,000 women die annually from heart disease, this fact is unknown to many women. Because heart disease is frequently preventable, increasing awareness of personal risk and preventative measures is a key element of health care for women. Nurse clinicians can evaluate, educate, and counsel women regarding their risk for this pervasive disease and promote behavior changes that will decrease that risk. Research evidence supports that lifestyle behaviors are the cornerstone of heart disease prevention. This article presents current evidence for the prevention of heart disease related to dietary intake, physical activity, weight management, smoking cessation, blood pressure control, and lipid management. Guidelines for implementing findings in clinical practice are discussed.

Cryopyrin-associated periodic syndromes: development of a patient-reported outcomes instrument to assess the pattern and severity of clinical disease activity.

PubMed

Hoffman, Hal M; Wolfe, Frederick; Belomestnov, Pavel; Mellis, Scott J

2008-09-01

Development of an instrument for characterization of symptom patterns and severity in patients with cryopyrin-associated periodic syndromes (CAPS). Two generations of daily health assessment forms (DHAFs) were evaluated in this study. The first-generation DHAF queried 11 symptoms. Analyses of results obtained with that instrument identified five symptoms included in a revised second-generation DHAF that was tested for internal consistency and test-retest reliability. This DHAF was also assessed during the initial portion of a phase 3 clinical study of CAPS treatment. Forty-eight CAPS patients provided data for the first-generation DHAFs. Five symptoms (rash, fever, joint pain, eye redness/pain, and fatigue) were included in the revised second-generation DHAF. Symptom severity was highly variable during all study phases with as many as 89% of patients reporting at least one symptom flare, and percentages of days with flares reaching 58% during evaluation of the second-generation instrument. Mean composite key symptom scores (KSSs) computed during evaluation of the second-generation DHAF correlated well with Physician's Global Assessment of Disease Activity (r=0.91, p<0.0001) and patient reports of limitations of daily activities (r=0.68, p<0.0001). Test-retest reliability and Cronbach's alpha's were high (0.93 and 0.94, respectively) for the second-generation DHAF. Further evaluation of this DHAF during a baseline period and placebo treatment in a phase 3 clinical study of CAPS patients indicated strong correlations between baseline KSS and Physician's Global Assessment of Disease Activity. Cronbach's alpha's at baseline and test-retest reliability were also high. Potentially important study limitations include small sample size, the lack of a standard tool for CAPS symptom assessment against which to validate the DHAF, and no assessment of the instrument's responsivity to CAPS therapy. The DHAF is a new instrument that may be useful for capturing symptom patterns and severity in CAPS patients and monitoring responses to therapies for these conditions.

IN VITRO EFFICACY OF EXTRACTS FROM PLANTS USED BY SMALL-HOLDER FARMERS IN THE TREATMENT OF DERMATOPHILOSIS IN CATTLE.

PubMed

Ndhlovu, Daud N; Masika, Patrick J

2017-01-01

Bovine dermatophilosis, an important skin disease of cattle caused by Dermatophilus congolensis , negatively impacts the livelihoods of small-holder farmers in Zimbabwe. This impact is through, morbidity, loss of draught animal power, costs incurred to manage the disease, losses associated with devalued damaged hides and the resultant culling of some of the affected cattle. Due to the inaccessibility of conventional drugs to manage bovine dermatophilosis, farmers have been reported to use local medicinal plants to manage the disease. The aim of the study was to evaluate the in vitro antimicrobial activities of three plants that small-holder farmers in Zimbabwe used to manage bovine dermatophilosis. Dried plant materials were ground into powder and extracted individually using, water, 80 % acetone and 80 % methanol. The antimicrobial properties of the plants were evaluated against two Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and one Gram-positive (Staphylococcus aureus) reference bacterial strains. They were further evaluated against a field isolate of Dermatophilus congolensis . The assays used were the disc diffusion, minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). Acetone and methanol extracts had superior inhibitory activities than did those of water. Pterocarpus angolensis DC extracts had better inhibitory properties with absolute MIC values of 0.156 - 5 mg/ml, Cissus Quadrangularis L had MIC values in the range 0.156 - 5 mg/ml while that of Catunaregam spinosa Thunb, Terveng was 0.156 - 10 mg/ml. Dermatophilus congolensis was more sensitive to Pterocarpus angolensis DC average MIC = 0.63 mg/ml than to Cissus quadrangularis L average MIC = 1.25 mg/ml and Catunaregam. spinosa Thunb, Terveng average MIC = 2.08 mg/ml. These results suggest the potential antibacterial activities of extracts of the three plants and hence farmers are, in a way, justified in using the plants. Better results (lower MIC) could be obtained by extracting and evaluating pure active compounds of the plants.

Performance of Crohn's disease Clinical Trial Endpoints based upon Different Cutoffs for Patient Reported Outcomes or Endoscopic Activity: Analysis of EXTEND Data.

PubMed

Feagan, Brian; Sandborn, William J; Rutgeerts, Paul; Levesque, Barrett G; Khanna, Reena; Huang, Bidan; Zhou, Qian; Maa, Jen-Fue; Wallace, Kori; Lacerda, Ana; Thakkar, Roopal B; Robinson, Anne M

2018-04-23

Clinical trial endpoints for Crohn's disease (CD) activity correlate poorly with mucosal inflammation; to assess treatment efficacy, patient-reported outcomes and endoscopic assessments are preferred. This study assessed the impact on treatment efficacy estimations of using different definitions of clinical and endoscopic remission and endoscopic response, and of using site- or central-based endoscopy evaluation. This post hoc analysis of data fromEXTEND (extend the safety and efficacy of adalimumab through endoscopic healing), a placebo (PBO)-controlled, randomized trial of adalimumab (ADA) for mucosal healing, included adults with moderate-to-severe CD. Subsets of patients meeting specified Simplified Endoscopic Score for CD (SES-CD) inclusion criteria, according to site or central reading, and baseline stool frequency (SF) and/or abdominal pain score (AP) thresholds were evaluated. Various endpoint definitions based on the Crohn's Disease Activity Index (CDAI), its SF and AP components, SES-CD, and composite endpoints were compared between treatment groups. Increased stringency of Week 12 clinical endpoints compared to CDAI<150 to SF≤3.0/1.5&AP≤1.0 reduced PBO response rates by ≥12% and increased treatment effects by ≤10%. Amending the SES-CD endpoint from ≤4 to ≤2 reduced the treatment effect from 24% to 8%. Composite endpoints further diminished response rates and effect sizes. Site-based evaluation was associated with lower remission rates versus central reading in the PBO group and, thus, greater ADA-related treatment effects. This analysis is the first to demonstrate that increasing the stringency of clinical and endoscopic endpoint definitions in CD trials, especially lowering SF or SES-CD definitions, reduces the ability to detect treatment-related change in CD activity; focus on endpoints that reflect clinical change is warranted.

Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer disease.

PubMed

Olazarán, J; Muñiz, R; Reisberg, B; Peña-Casanova, J; del Ser, T; Cruz-Jentoft, A J; Serrano, P; Navarro, E; García de la Rocha, M L; Frank, A; Galiano, M; Fernández-Bullido, Y; Serra, J A; González-Salvador, M T; Sevilla, C

2004-12-28

To evaluate the efficacy of a cognitive-motor program in patients with early Alzheimer disease (AD) who are treated with a cholinesterase inhibitor (ChEI). Patients with mild cognitive impairment (MCI) (12), mild AD (48), and moderate AD (24) (Global Deterioration Scale stages 3, 4, and 5) were randomized to receive psychosocial support plus cognitive-motor intervention (experimental group) or psychosocial support alone (control group). Cognitive-motor intervention (CMI) consisted of a 1-year structured program of 103 sessions of cognitive exercises, plus social and psychomotor activities. The primary efficacy measure was the cognitive subscale of the AD Assessment Scale (ADAS-cog). Secondary efficacy measures were the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Geriatric Depression Scale. Evaluations were conducted at 1, 3, 6, and 12 months by blinded evaluators. Patients in the CMI group maintained cognitive status at month 6, whereas patients in the control group had significantly declined at that time. Cognitive response was higher in the patients with fewer years of formal education. In addition, more patients in the experimental group maintained or improved their affective status at month 12 (experimental group, 75%; control group, 47%; p = 0.017). A long-term CMI in ChEI-treated early Alzheimer disease patients produced additional mood and cognitive benefits.

Oxidative stress status in patients with melasma.

PubMed

Seçkin, Havva Yıldız; Kalkan, Göknur; Baş, Yalçın; Akbaş, Ali; Önder, Yalçın; Özyurt, Hüseyin; Sahin, Mehmet

2014-09-01

Melasma is an acquired skin disease characterized clinically by development of gray-brown macules or patches. The lesions have geographic borders and most often seen on face and less frequently on the neck and forearms. Pathogenesis has not been completely understood yet. Although the disease constitutes a very disturbing cosmetic problem, it has not obtained an efficient treatment. There were not any studies in the literature that evaluates the role of oxidative stress in melasma. The evaluation of the role of oxidative stress in melasma. Fifty melasma patients and 50 healthy volunteers were included in the study. The diagnosis was made clinically and the patients were evaluated by Melasma Area Severity Index. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) enzyme activities and malondialdehyde, nitric oxide, protein carbonyl levels were measured both in the melasma group and the control group. SOD and GSH-Px enzyme activities were significantly higher in the patient group in comparison with the control group (p < 0.001). Protein carbonyl levels were significantly lower in the patient group (p < 0.001). The results show that the balance between oxidant and anti-oxidants was disrupted and the oxidative stress increased in melasma. These results improve the understanding of etiology-pathogenesis of the disease and its treatment.

Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk.

PubMed

Cugno, Massimo; Tedeschi, Alberto; Borghi, Alessandro; Bucciarelli, Paolo; Asero, Riccardo; Venegoni, Luigia; Griffini, Samantha; Grovetti, Elena; Berti, Emilio; Marzano, Angelo Valerio

2015-01-01

Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease.

Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk

PubMed Central

Cugno, Massimo; Tedeschi, Alberto; Borghi, Alessandro; Bucciarelli, Paolo; Asero, Riccardo; Venegoni, Luigia; Griffini, Samantha; Grovetti, Elena; Berti, Emilio; Marzano, Angelo Valerio

2015-01-01

Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease. PMID:26057532

Antimycobacterial activity of pyrazinoate prodrugs in replicating and non-replicating Mycobacterium tuberculosis.

PubMed

Segretti, Natanael Dante; Simões, Cristina Kortstee; Corrêa, Michelle Fidelis; Felli, Veni Maria Andres; Miyata, Marcelo; Cho, Sang Hyun; Franzblau, Scott Gary; Fernandes, João Paulo Dos Santos

2016-07-01

Tuberculosis (TB) is an important infectious disease caused by Mycobacterium tuberculosis (Mtb) and responsible for thousands of deaths every year. Although there are antimycobacterial drugs available in therapeutics, just few new chemical entities have reached clinical trials, and in fact, since introduction of rifampin only two important drugs had reached the market. Pyrazinoic acid (POA), the active agent of pyrazinamide, has been explored through prodrug approach to achieve novel molecules with anti-Mtb activity, however, there is no activity evaluation of these molecules against non-replicating Mtb until the present. Additionally, pharmacokinetic must be preliminary evaluated to avoid future problems during clinical trials. In this paper, we have presented six POA esters as prodrugs in order to evaluate their anti-Mtb activity in replicating and non-replicating Mtb, and these showed activity highly influenced by medium composition (especially by albumin). Lipophilicity seems to play the main role in the activity, possibly due to controlling membrane passage. Novel duplicated prodrugs of POA were also described, presenting interesting activity. Cytotoxicity of these prodrugs set was also evaluated, and these showed no important cytotoxic profile. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antibiotic-producing Pseudomonas fluorescens mediates rhizome rot disease resistance and promotes plant growth in turmeric plants.

PubMed

Prabhukarthikeyan, S R; Keerthana, U; Raguchander, T

2018-05-01

Rhizome rot of turmeric caused by Pythium aphanidermatum is a major threat to turmeric-cultivating areas of India. This study intends to evaluate the performance of fluorescent pseudomonads against Rhizome rot disease and understand the resistance mechanism in Turmeric plants. Fluorescent pseudomonads were screened against Pythium aphanidermatum using dual culture. Selected strains were evaluated for the performance of growth promoting attributes and the presence of antibiotic genes through PCR analysis. Strain FP7 recorded the maximum percent inhibition of P. aphanidermatum under in vitro conditions. Strains FP7 and TPF54 both increased plant growth in turmeric plants in vitro. Strain FP7 alone contained all the evaluated antibiotic biosynthetic genes. Talc and liquid-based formulations were prepared with effective strain and tested for its biocontrol activities under both glasshouse and field conditions. Enzymatic activities of the induced defense enzymes such as PO, PPO, PAL, CAT and SOD were estimated and subjected to spectrophotometric analysis. A combination of rhizome dip and soil drench of FP7 liquid formulation treatment remarkably recorded the minimum disease incidence, higher defense enzymes, maximum plant growth and yield under glasshouse and field conditions. Application of strain FP7 increased the defense molecules, plant growth and yield in turmeric plants thereby reducing the incidence of rhizome rot disease. Moreover, this study has a potential to be adopted for sustainable and eco-friendly turmeric production. Copyright © 2018 Elsevier GmbH. All rights reserved.

Outcomes of active surveillance for the management of clinically localized prostate cancer in the prospective, multi-institutional Canary PASS cohort

PubMed Central

Newcomb, Lisa F.; Thompson, Ian M.; Boyer, Hilary D.; Brooks, James D.; Carroll, Peter R.; Cooperberg, Matthew R.; Dash, Atreya; Ellis, William J.; Fazli, Ladan; Feng, Ziding; Gleave, Martin E.; Kunju, Priya; Lance, Raymond S.; McKenney, Jesse K.; Meng, Maxwell V.; Nicolas, Marlo M.; Sanda, Martin G.; Simko, Jeffry; So, Alan; Tretiakova, Maria S.; Troyer, Dean A.; True, Lawrence D.; Vakar-Lopez, Funda; Virgin, Jeff; Wagner, Andrew A.; Wei, John T.; Zheng, Yingye; Nelson, Peter S.; Lin, Daniel W.

2016-01-01

Purpose Active surveillance represents a strategy to address the overtreatment of prostate cancer, yet uncertainty regarding individual patient outcomes remains a concern. We evaluated outcomes in a prospective multi-center study of active surveillance. Methods We studied 905 men in the prospective Canary Prostate cancer Active Surveillance Study (PASS) enrolled between 2008 to 2013. We collected clinical data at study entry and at pre-specified intervals and determined associations with adverse reclassification defined as increased Gleason grade or greater cancer volume on follow-up biopsy. We also evaluated the relationships of clinical parameters with pathology findings in participants who underwent surgery after a period of active surveillance. Results During a median follow-up of 28 months, 24% of participants experienced adverse reclassification, of whom 53% underwent treatment while 31% continued active surveillance. Overall, 19% of participants received treatment, 68% with adverse reclassification while 32% opted for treatment without disease reclassification. In multivariate Cox proportional hazards modeling, percent of biopsy cores with cancer, BMI, and PSA density were associated with adverse reclassification (P = 0.01, 0.04, 0.04). Of 103 participants subsequently treated by radical prostatectomy, 34% had adverse pathology, defined as primary pattern 4–5 or non-organ confined disease, including two with positive lymph nodes, with no significant relationship between risk category at diagnosis and findings at surgery (P = 0.76). Conclusion Most men remain on active surveillance at five years without adverse reclassification or adverse pathology at surgery. However, clinical factors had only modest association with disease reclassification, supporting the need for approaches that improve prediction of this outcome. PMID:26327354

Pilot of the Chronic Disease Self-Management Program (CDSMP) for Adolescents and Young Adults with Sickle Cell Disease

PubMed Central

Crosby, Lori E.; Joffe, Naomi E.; Peugh, James; Ware, Russell E.; Britto, Maria T.

2016-01-01

Purpose This study evaluated the feasibility of a group self-management intervention, the well-established Stanford Chronic Disease Self-Management Program (CDSMP), for adolescents and young adults (AYA) with sickle cell disease (SCD). Methods A total of 22 AYA participants with SCD, ages 16 to 24 years, completed self-efficacy and quality of life (HRQOL) measures before the CDSMP, after, and 3 and 6 months later. Results This AYA cohort showed significant improvements in self-efficacy (primary outcome) after the intervention. Analyses of follow-up data revealed a medium effect of the CDSMP on patient activation 3 months post although this was not sustained. Participants were highly satisfied, but only 64% completed the program. Conclusions This study demonstrates that the CDSMP is acceptable, and has the ability to improve self-efficacy. Additional research is needed to determine feasibility and evaluate health outcomes for AYA with SCD. PMID:27793727

Depressive symptoms and perception of quality of life in Parkinson's disease.

PubMed

Scalzo, Paula; Kummer, Arthur; Cardoso, Francisco; Teixeira, Antonio Lucio

2009-06-01

Depression has been proposed as a major contributor to poor quality of life (QoL) in Parkinson's disease (PD). To evaluate the relationship between depressive symptoms and QoL in subjects with PD. Beck Depression Inventary (BDI) was used to evaluate depressive symptoms and Parkinson's Disease Quality of Life Questionnaire (PDQ-39) to assess the perception of the QoL. Thirty seven patients (19 male/ 18 female) with a typical onset PD and mean disease duration of 7.7 years were studied. Higher scores on BDI correlated with poorer perception of the QoL. This association occurred at the expense of the following PDQ39 domains: mobility, activities of daily living, social support, cognition and emotional well-being dimensions. PD severity also correlated with QoL. Our study corroborates the assumption that depressive symptoms contributed significantly to QoL in PD.

Penile Mondor's disease after anterolateral retroperitoneal approach for lumbar fracture.

PubMed

Dobran, Mauro; Benigni, Roberta; Nasi, Davide; Cantoro, Daniele

2017-11-01

This is a rare case of thrombosis of the dorsal vein of the penis (Mondor's disease) occurred after an anterior-lateral retroperitoneal approach for a vertebral stabilisation in thoracolumbar vertebral fracture. Potential causes are traumatism, neoplasms, excessive sexual activity or abstinence. Although penile Mondor's disease is a clinical diagnosis, ultrasound imaging is the gold standard to confirm it. In the reported case, 1 week after neurosurgical retroperitoneal procedure of vertebral stabilisation, the patient complained of a painful cord-like mass midshaft of penis. The diagnosis was made by clinical evaluation and ultrasound images. After 2 weeks of therapy with enoxaparin sodium, the patient recovered. The authors report this case evaluating the possible correlation between the anterior-lateral retroperitoneal approach and the development of the rare Mondor's disease. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Biochemical markers in the assessment of bone disease

NASA Technical Reports Server (NTRS)

Bikle, D. D.

1997-01-01

As the mean age of our population increases, increasing attention has been paid to the diseases associated with aging, including diseases of the skeleton such as osteoporosis. Effective means of treating and possibly preventing such skeletal disorders are emerging, making their early recognition an important goal for the primary care physician. Although bone density measurements and skeletal imaging studies remain of primary diagnostic importance in this regard, a large number of assays for biochemical markers of bone formation and resorption are being developed that promise to complement the densitometry measurements and imaging studies, providing an assessment of the rates of bone turnover and an earlier evaluation of the effects of therapy. In this review, emphasizing the recent literature, the major biochemical markers currently in use or under active investigation are described, and their application in a number of diseases of the skeleton including osteoporosis is evaluated.

Development of criteria for evaluating clinical response in thyroid eye disease using a modified Delphi technique.

PubMed

Douglas, Raymond S; Tsirbas, Angelo; Gordon, Mark; Lee, Diana; Khadavi, Nicole; Garneau, Helene Chokron; Goldberg, Robert A; Cahill, Kenneth; Dolman, Peter J; Elner, Victor; Feldon, Steve; Lucarelli, Mark; Uddin, Jimmy; Kazim, Michael; Smith, Terry J; Khanna, Dinesh

2009-09-01

To identify components of a provisional clinical response index for thyroid eye disease using a modified Delphi technique. The International Thyroid Eye Disease Society conducted a structured, 3-round Delphi exercise establishing consensus for a core set of measures for clinical trials in thyroid eye disease. The steering committee discussed the results in a face-to-face meeting (nominal group technique) and evaluated each criterion with respect to its feasibility, reliability, redundancy, and validity. Redundant measures were consolidated or excluded. Criteria were parsed into 11 domains for the Delphi surveys. Eighty-four respondents participated in the Delphi 1 survey, providing 220 unique items. Ninety-two members (100% of the respondents from Delphi 1 plus 8 new participants) responded in Delphi 2 and rated the same 220 items. Sixty-four members (76% of participants) rated 153 criteria in Delphi 3 (67 criteria were excluded because of redundancy). Criteria with a mean greater than 6 (1 = least appropriate to 9 = most appropriate) were further evaluated by the nominal group technique and provisional core measures were chosen. Using a Delphi exercise, we developed provisional core measures for assessing disease activity and severity in clinical trials of therapies for thyroid eye disease. These measures will be iteratively refined for use in multicenter clinical trials.

Anti-angiogenic activity of Entada africana root.

PubMed

Germanò, Maria Paola; Certo, Giovanna; D'Angelo, Valeria; Sanogo, Rokia; Malafronte, Nicola; De Tommasi, Nunziatina; Rapisarda, Antonio

2015-01-01

Entada africana roots are used in African traditional medicine for various diseases including inflammation. This application may be mediated through anti-angiogenic effects. Thus, in this study the anti-angiogenic activity of E. africana root extracts (n-hexane, chloroform, chloroform/methanol and methanol) was preliminarily evaluated by the quantitative determination of endogenous alkaline phosphatase in zebrafish embryos. A bioactivity-guided fractionation of chloroform/methanol extract yielded apigenin and robinetin as the main constituents from the most active fractions. In addition, a marked reduction on capillary formation was evidenced in chick chorioallantoic membrane after treatment with the active fractions or isolated compounds. Results obtained in this study suggest that the anti-angiogenic effects of E. africana root may account for its use in inflammatory diseases and other related pathological conditions.

Weight Status, Physical Activity, and Fitness among Third-Grade Rural Children

ERIC Educational Resources Information Center

Shriver, Lenka H.; Harrist, Amanda W.; Hubbs-Tait, Laura; Topham, Glade; Page, Melanie; Barrett, Aimee

2011-01-01

Background: Rural children are at a particular high risk for obesity. Given the importance of exercise in obesity and chronic disease prevention, this study evaluated the level and relationship between physical activity and fitness in a sample of rural third graders. The second purpose of the study was to determine potential differences in…

Trypanocide, cytotoxic, and antifungal activities of Momordica charantia.

PubMed

Santos, Karla K A; Matias, Edinardo F F; Sobral-Souza, Celestina E; Tintino, Saulo R; Morais-Braga, Maria F B; Guedes, Glaucia M M; Santos, Francisco A V; Sousa, Ana Carla A; Rolón, Miriam; Vega, Celeste; de Arias, Antonieta Rojas; Costa, José G M; Menezes, Irwin R A; Coutinho, Henrique D M

2012-02-01

Chagas disease, caused by Trypanosoma cruzi, is a public health problem. Currently, chemotherapy is the only available treatment for this disease, and the drugs used, nifurtimox and benzonidazol, present high toxicity levels. An alternative for replacing these drugs are natural extracts from Momordica charantia L. (Cucurbitaceae) used in traditional medicine because of their antimicrobial and biological activities. In this study, we evaluated the extract of M. charantia for its antiepimastigote, antifungal, and cytotoxic activities. An ethanol extract of leaves from M. charantia was prepared. To research in vitro antiepimastigote activity, T. cruzi CL-B5 clone was used. Epimastigotes were inoculated at a concentration of 1 × 10(5) cells/mL in 200 µl tryptose-liver infusion. For the cytotoxicity assay, J774 macrophages were used. The antifungal activity was evaluated by microdilution using strains of Candida albicans, Candida tropicalis, and Candida krusei. The effective concentration capable of killing 50% of parasites (IC(50)) was 46.06 µg/mL. The minimum inhibitory concentration (MIC) was ≤ 1024 µg/mL. Metronidazole showed a potentiation of its antifungal effect when combined with an extract of M. charantia. Our results indicate that M. charantia could be a source of plant-derived natural products with antiepimastigote and antifungal-modifying activity with moderate toxicity.

Antidepressive-like effects and antioxidant activity of green tea and GABA green tea in a mouse model of post-stroke depression.

PubMed

Di Lorenzo, Arianna; Nabavi, Seyed Fazel; Sureda, Antoni; Moghaddam, Akbar Hajizadeh; Khanjani, Sedigheh; Arcidiaco, Patrizia; Nabavi, Seyed Mohammad; Daglia, Maria

2016-03-01

Growing evidence suggests that oxidative stress plays a role in the development of chronic diseases such as cardiovascular disease and some psychiatric disorders. Tea consumption exerts beneficial effects against damage induced by cerebral ischemia-reperfusion in ischemic stroke and depressive symptoms in depression. The aim of this study was to evaluate, in vivo, the protective activity of green tea (GT) and GABA green tea (GGT) against post-stroke depression (PSD), a common consequence of stroke. The antidepressive-like effects of GT and GGT were determined by behavioral tests in a mouse model of post-stroke depression. The antioxidant activity was evaluated by GSH, SOD, and TBARS measurements on mouse brain. The chemical composition of tea extracts was characterized through chromatographic methods. GGT and GT resulted active in the modulation of depressive symptoms and the reduction of oxidative stress, restoring normal behavior, and at least in part, antioxidant endogenous defenses. The higher polyphenol, theanine, glutamine, and caffeine content may justify the higher activity found in GGT. This work represents the first attempt to demonstrate the positive effect of tea, and especially GGT, on post-stroke depression and to correlate this effect with the antioxidant activity and phytochemical composition of tea. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Immunomodulatory effects of the aromatic geranyl derivative filifolinone tested by the induction of cytokine expression.

PubMed

Valenzuela, Beatriz; Imarai, Mónica; Torres, René; Modak, Brenda

2013-12-01

Fish farming crops are constantly exposed to infectious diseases due to intensive production conditions under which microorganisms develop and spread easily, resulting in severe economic losses. The massive use of antibiotics to control these diseases has lead to the accumulation of residues and the development of drug resistance. Consequently, it is urgent to develop new pharmacological tools to stimulate protective immune responses in salmonids to combat infectious diseases. We evaluated the immunostimulant activity of terpenoid derivatives isolated from species of the Heliotropium genus, which had previously shown antiviral activity in salmon. The immunomodulatory effects of the 3 H-spiro [1-benzofuran-2,1'-ciclohexane] derivative called filifolinone, were studied in vitro using the SHK-1 cell line derived from leucocytes of salmon head kidney and in vivo in Atlantic salmon. For the evaluation, we studied the effect of this compound in the expression of various cytokines. The results showed that Filifolinone increases the levels of expression of pro-inflammatory and anti-inflammatory cytokines. This suggests that Filifolinone is a potential alternative immunomodulator for veterinary purposes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Orbital flourine-18-fluorodeoxyglucose positron emission tomography in patients with Graves' disease for evaluation of active inflammation.

PubMed

Uslu-Beşli, Lebriz; Kabasakal, Levent; Sağer, Sait; Cicik, Erdoğan; Asa, Sertaç; Sönmezoğlu, Kerim

2017-11-01

Prediction and early diagnosis of orbitopathy is needed in patients with Graves' disease, especially when radioiodine therapy is planned. Positron emission tomography/computerized tomography (PET/CT) using flourine-18-fluorodeoxyglucose (FDG) is an effective imaging modality in detection of inflammation, however, its ability to detect orbital inflammation has not been well studied. The aim of our study is to determine the ability of FDG PET/CT to detect orbital inflammation related with Graves' disease, identify active orbitopathy, predict the radioiodine-triggered orbitopathy, and find out the effects of radioiodine on orbital inflammation. Total 31 Graves' disease patients and 17 controls were included. All Graves' disease patients underwent cranial FDG PET/CT imaging prior therapy. Radioiodine therapy and post-treatment PET/CT study was applied to 21 patients. PET/CT images of all examinees were evaluated, measuring extraocular muscle maximum standard uptake value (SUVmax) and muscle thickness. FDG uptake was increased in the majority of extraocular muscles in Graves' disease patients in comparison to controls and this increase was found to be irrelevant from muscle thickness. Extraocular muscle SUVmax values did not increase in Graves' orbitopathy patients who received radioiodine under corticosteroid prophylaxis. SUVmax level of all orbital rectus muscles were increased after radioiodine therapy in nonsmokers, whereas no increase was detected in smokers. FDG PET/CT may be helpful in detection of extraocular muscle inflammation and it may show ongoing orbitopathy in early stages of inflammation before anatomical changes occur.

An Examination of the Reliability and Factor Structure of the Physical Activity Scale for Individuals With Physical Disabilities (PASIPD) Among Individuals Living With Parkinson's Disease.

PubMed

Jimenez-Pardo, J; Holmes, J D; Jenkins, M E; Johnson, A M

2015-07-01

Physical activity is generally thought to be beneficial to individuals with Parkinson's disease (PD). There is, however, limited information regarding current rates of physical activity among individuals with PD, possibly due to a lack of well-validated measurement tools. In the current study we sampled 63 individuals (31 women) living with PD between the ages of 52 and 87 (M = 70.97 years, SD = 7.53), and evaluated the amount of physical activity in which they engaged over a 7-day period using a modified form of the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD). The PASIPD was demonstrated to be a reliable measure within this population, with three theoretically defensible factors: (1) housework and home-based outdoor activities; (2) recreational and fitness activities; and (3) occupational activities. These results suggest that the PASIPD may be useful for monitoring physical activity involvement among individuals with PD, particularly within large-scale questionnaire-based studies.

Interleukin 35 (IL-35) and IL-37: Intestinal and peripheral expression by T and B regulatory cells in patients with Inflammatory Bowel Disease.

PubMed

Fonseca-Camarillo, Gabriela; Furuzawa-Carballeda, Janette; Yamamoto-Furusho, Jesús K

2015-10-01

The aim of the study was to characterize and to quantify peripheral and tissue. IL-35- and IL-37-producing cells in Inflammatory Bowel Disease (IBD) patients. We studied a total of 38 active UC, 31 inactive UC, 17 active CD, and 13 inactive CD and 50 non-inflamed tissues as control group. Gene expression was measured by real time polymerase chain reaction (RT-PCR) and protein expression was evaluated in tissue by immunohistochemistry and in peripheral blood mononuclear cells by flow cytometry. Higher levels of IL-35 was produced by intestinal regulatory B cells and circulating regulatory CD4(+) and CD8(+) T cells in active vs. inactive disease or healthy donors (P<0.05). The IL-37 was conspicuously synthesized by circulating B cells, active natural killer cells and monocytes. These results suggest that down-regulation of inflammation in active IBD patients might be based on the increased expression of IL-35 and IL-37. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cognitive slowing in Parkinson disease is accompanied by hypofunctioning of the striatum.

PubMed

Sawamoto, N; Honda, M; Hanakawa, T; Aso, T; Inoue, M; Toyoda, H; Ishizu, K; Fukuyama, H; Shibasaki, H

2007-03-27

To investigate whether cognitive slowing in Parkinson disease (PD) reflects disruption of the basal ganglia or dysfunction of the frontal lobe by excluding an influence of abnormal brain activity due to motor deficits. We measured neuronal activity during a verbal mental-operation task with H(2)(15)O PET. This task enabled us to evaluate brain activity change associated with an increase in the cognitive speed without an influence on motor deficits. As the speed of the verbal mental-operation task increased, healthy controls exhibited proportional increase in activities in the anterior striatum and medial premotor cortex, suggesting the involvement of the corticobasal ganglia circuit in normal performance of the task. By contrast, patients with PD lacked an increase in the striatal activity, whereas the medial premotor cortex showed a proportional increase. Although the present study chose a liberal threshold and needs subsequent confirmation, the findings suggest that striatal disruption resulting in abnormal processing in the corticobasal ganglia circuit may contribute to cognitive slowing in Parkinson disease, as is the case in motor slowing.

Traditional Chinese Medicine Improves Activities of Daily Living in Parkinson's Disease

PubMed Central

Pan, Weidong; Kwak, Shin; Liu, Yun; Sun, Yan; Fang, Zhenglong; Qin, Baofeng; Yamamoto, Yoshiharu

2011-01-01

We evaluated the effects of a traditional Chinese medicine (TCM), named Zeng-xiao An-shen Zhi-chan 2 (ZAZ2), on patients with Parkinson's disease (PD). Among 115 patients with idiopathic PD enrolled (mean age, 64.7 ± 10.2 years old), 110 patients (M = 65, F = 45; mean age, 64.9 ± 10.7 years old) completed the study. Patients took either ZAZ2 (n = 59) or placebo granule (n = 56) in a blind manner for 13 weeks while maintaining other anti-Parkinson medications unchanged. All participants wore a motion logger, and we analyzed the power-law temporal autocorrelation of the motion logger records taken on 3 occasions (before, one week, and 13 weeks after the drug administration). Drug efficacy was evaluated with the conventional Unified Parkinson Disease Rating Scale (UPDRS), as well as the power-law exponent α, which corresponds to the level of physical activity of the patients. ZAZ2 but not placebo granule improved the awake-sleep rhythm, the UPDRS Part II, Part II + III, and Part IV scores, and the α values. The results indicate that ZAZ2 improved activities of daily living (ADL) of parkinsonism and, thus, is a potentially suitable drug for long-term use. PMID:21687764

Clinical Epidemiology, Evaluation, and Management of Dementia in Parkinson Disease.

PubMed

Safarpour, Delaram; Willis, Allison W

2016-11-01

The prevalence of neurodegenerative diseases such as Parkinson disease (PD) will increase substantially, due to the aging of the population and improved treatments leading to better disease-related outcomes. Dementia is the most common nonmotor symptom in PD, and most patients with PD will have cognitive dysfunction and cognitive decline in the course of their disease. The development of cognitive dysfunction in PD greatly limits the ability to participate in activities of daily living and can be a tipping point for nursing home placement or major caregiver stress. Understanding the different causes of dementia and how to reduce the incidence and impact of secondary cognitive dysfunction in PD are necessary skills for primary care physicians and neurologists. In this review, we discuss the clinical epidemiology of dementia in PD with an emphasis on preventable cognitive dysfunction, present tools for outpatient evaluation of cognitive dysfunction, and describe current pharmacological treatments for dementia in PD. © The Author(s) 2016.

Gamma delta T cell responses associated with the development of tuberculosis in health care workers.

PubMed

Ordway, Diane J; Pinto, Luisa; Costa, Leonor; Martins, Marta; Leandro, Clara; Viveiros, Miguel; Amaral, Leonard; Arroz, Maria J; Ventura, Fernando A; Dockrell, Hazel M

2005-03-01

This study evaluated T cell immune responses to purified protein derivative (PPD) and Mycobacterium tuberculosis (Mtb) in health care workers who remained free of active tuberculosis (HCWs w/o TB), health care workers who went on to develop active TB (HCWs w/TB), non-health care workers who were TB free (Non-HCWs) and tuberculosis patients presenting with minimal (Min TB) or advanced (Adv TB) disease. Peripheral blood mononuclear cells (PBMC) were stimulated with Mtb and PPD and the expression of T cell activation markers CD25+ and HLA-DR+, intracellular IL-4 and IFN-gamma production and cytotoxic responses were evaluated. PBMC from HCWs who developed TB showed decreased percentages of cells expressing CD8+CD25+ in comparison to HCWs who remained healthy. HCWs who developed TB showed increased gammadelta TCR+ cell cytotoxicity and decreased CD3+gammadelta TCR- cell cytotoxicity in comparison to HCWs who remained healthy. PBMC from TB patients with advanced disease showed decreased percentages of CD25+CD4+ and CD25+CD8+ T cells that were associated with increased IL-4 production in CD8+ and gammadelta TCR+ phenotypes, in comparison with TB patients presenting minimal disease. TB patients with advanced disease showed increased gammadelta TCR+ cytotoxicity and reduced CD3+gammadelta TCR- cell cytotoxicity. Our results suggest that HCWs who developed TB show an early compensatory mechanism involving an increase in lytic responses of gammadelta TCR+ cells which did not prevent TB.

Neuroendocrine evaluation of cardiac disease.

PubMed

Sisson, D David

2004-09-01

Current evidence favors the view that regardless of etiology, there is a predictable sequence of neuroendocrine activation that operates in most dogs and cats with progressive heart disease and that it is largely, but not entirely, independent of etiology. The natriuretic peptides and sympathetic nervous system seem to be early responders to developing cardiac and hemodynamic perturbations in both species. BNP plays a particularly prominent role in cats, possibly as a reflection of disease etiology. Shortly thereafter, plasma endothelin concentrations rise, reflecting the impact of the hemodynamic alterations on the vasculature. Endothelin and the natriuretic peptides directly suppress plasma renin release but have divergent effects on aldosterone. Activation of the tissue RAAS may operate early on to further the progression of heart failure, but evidence of plasma RAAS activation occurs comparatively late and near the time of development of overt CHF. Finally, in animals with severe CHF that are prone to hypotension,vasopressin levels may also rise, contributing to the retention of free water and congestion that is refractory to diuretics. Although oversimplified, this scenario seems to be consistent with data obtained in human, canine, and feline patients. These observations provide some impetus for evaluating ACE inhibitors in cats and beta-receptor-blocking drugs in dogs and cats. Perhaps we are also a little closer to identifying useful biochemical markers that can aid in the diagnosis of heart disease, guide therapy, and improve our understanding of the biologic processes occurring in our patients. Copyright 2004 Elsevier Inc.

Evidence for adaptive cortical changes in swallowing in Parkinson's disease.

PubMed

Suntrup, Sonja; Teismann, Inga; Bejer, Joke; Suttrup, Inga; Winkels, Martin; Mehler, David; Pantev, Christo; Dziewas, Rainer; Warnecke, Tobias

2013-03-01

Dysphagia is a relevant symptom in Parkinson's disease, whose pathophysiology is poorly understood. It is mainly attributed to degeneration of brainstem nuclei. However, alterations in the cortical contribution to deglutition control in the course of Parkinson's disease have not been investigated. Here, we sought to determine the patterns of cortical swallowing processing in patients with Parkinson's disease with and without dysphagia. Swallowing function in patients was objectively assessed with fiberoptic endoscopic evaluation. Swallow-related cortical activation was measured using whole-head magnetoencephalography in 10 dysphagic and 10 non-dysphagic patients with Parkinson's disease and a healthy control group during self-paced swallowing. Data were analysed applying synthetic aperture magnetometry, and group analyses were done using a permutation test. Compared with healthy subjects, a strong decrease of cortical swallowing activation was found in all patients. It was most prominent in participants with manifest dysphagia. Non-dysphagic patients with Parkinson's disease showed a pronounced shift of peak activation towards lateral parts of the premotor, motor and inferolateral parietal cortex with reduced activation of the supplementary motor area. This pattern was not found in dysphagic patients with Parkinson's disease. We conclude that in Parkinson's disease, not only brainstem and basal ganglia circuits, but also cortical areas modulate swallowing function in a clinically relevant way. Our results point towards adaptive cerebral changes in swallowing to compensate for deficient motor pathways. Recruitment of better preserved parallel motor loops driven by sensory afferent input seems to maintain swallowing function until progressing neurodegeneration exceeds beyond the means of this adaptive strategy, resulting in manifestation of dysphagia.

Awareness of Cardiovascular Disease and Preventive Behaviors Among Overweight Immigrant Latinas.

PubMed

Koniak-Griffin, Deborah; Brecht, Mary-Lynn

2015-01-01

Low-income Latina women face increased risk for cardiovascular disease (CVD) due to high rates of obesity, diabetes, and other comorbidities. Language barriers, lack of health insurance, and lack of access to preventive health messages may further increase their risk. The purpose of this study was to evaluate knowledge about CVD of overweight, immigrant Latinas who spoke little or no English and participated in an educational intervention. Ninety participants completed a CVD knowledge questionnaire before and after 8 educational sessions based upon Su Corazón, Su Vida. The curriculum focused on understanding risk factors of CVD and prevention through heart-healthy diets, physical activity, and weight control. The questionnaire evaluated general CVD knowledge (eg, heart disease is the leading cause of death in women) and prevention measures (eg, physical activity can lower a woman's risk for getting heart disease). Data were analyzed using generalized estimating equations and correlational statistics. Participants were middle-aged, overweight Latinas, predominantly of Mexican descent, with low education and acculturation. Baseline knowledge that heart disease is the leading cause of death in women was low. A comparison of preintervention and postintervention scores on the questionnaire showed a significant change (P < 0.001), with means of 7.9 and 9.4, respectively. Scores for individual items correctly answered significantly improved for 9 of the 11 items, including questions about portion control to lose weight, physical activity, overweight, and risk for heart disease. Most participants did not recognize that men and women may experience different symptoms of a heart attack. Knowledge was not significantly related to background characteristics, body mass index, or lifestyle behaviors. Despite campaigns to increase CVD awareness, many Spanish-speaking, immigrant Latinas remain unaware that heart disease is the leading cause of death. Educational interventions may significantly improve their CVD knowledge; nonetheless, continued cardiovascular health promotion efforts are needed for this population.

Transgenic animal models of neurodegeneration based on human genetic studies

PubMed Central

Richie, Christopher T.; Hoffer, Barry J.; Airavaara, Mikko

2011-01-01

The identification of genes linked to neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Parkinson's disease (PD) has led to the development of animal models for studying mechanism and evaluating potential therapies. None of the transgenic models developed based on disease-associated genes have been able to fully recapitulate the behavioral and pathological features of the corresponding disease. However, there has been enormous progress made in identifying potential therapeutic targets and understanding some of the common mechanisms of neurodegeneration. In this review, we will discuss transgenic animal models for AD, ALS, HD and PD that are based on human genetic studies. All of the diseases discussed have active or complete clinical trials for experimental treatments that benefited from transgenic models of the disease. PMID:20931247

Bioactive components, antioxidant and DNA damage inhibitory activities of honeys from arid regions.

PubMed

Habib, Hosam M; Al Meqbali, Fatima T; Kamal, Hina; Souka, Usama D; Ibrahim, Wissam H

2014-06-15

Honey serves as a good source of natural antioxidants, which are effective in reducing the risk of occurrence of several diseases. This study was undertaken to address the limited knowledge regarding the polyphenolic content, antioxidant and DNA damage inhibitory activities of honeys produced in arid regions and compare them with well-recognized honeys from non-arid regions. Different types of honey were assessed for their contents of total phenolics, total flavonoids, and certain types of phenolic compounds. The antioxidant capacity of honey was evaluated by ferric-reducing/antioxidant power assay (FRAP), free radical-scavenging activity (DPPH), nitric oxide (NO) radical-scavenging assay, total antioxidant activity, and DNA damage. Results clearly showed significant differences among honeys with all the evaluated parameters. Results also showed that one or more types of honey from arid regions contained higher levels of phenolic compounds, free radical-scavenging activities, or DNA damage inhibitory activities compared with the evaluated honeys from non-arid regions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Visual Acuity’s Association with Levels of Leisure-Time Physical Activity Among Community-Dwelling Older Adults

PubMed Central

Swanson, Mark W; Bodner, Eric; Sawyer, Patricia; Allman, Richard

2013-01-01

Little is known about the affect of reduced vision on physical activity in older adults. This study evaluates the association of visual acuity level, self-reported vision and ocular disease conditions with leisure-time physical activity and calculated caloric expenditure. A cross sectional study of 911 subjects 65 yr and older from the University of Alabama at Birmingham Study of Aging (SOA) cohort was conducted evaluating the association of vision-related variables to weekly kilocalorie expenditure calculated from the 17-item Leisure Time Physical Activity Questionnaire. Ordinal logistic regression was used to evaluate possible associations controlling for potential confounders. In multivariate analyses, each lower step in visual acuity category below 20/50 was significantly associated with reduced odds of having a higher level of physical activity OR 0.81, 95% CI 0.67, 0.97. Reduced visual acuity appears to be independently associated with lower levels of physical activity among community-dwelling adults. PMID:21945888

Degenerative spinal disease in large felids.

PubMed

Kolmstetter, C; Munson, L; Ramsay, E C

2000-03-01

Degenerative spinal disorders, including intervertebral disc disease and spondylosis, seldom occur in domestic cats. In contrast, a retrospective study of 13 lions (Panthera leo), 16 tigers (Panthera tigris), 4 leopards (Panthera pardis), 1 snow leopard (Panthera uncia), and 3 jaguars (Panthera onca) from the Knoxville Zoo that died or were euthanatized from 1976 to 1996 indicated that degenerative spinal disease is an important problem in large nondomestic felids. The medical record, radiographic data, and the necropsy report of each animal were examined for evidence of intervertebral disc disease or spondylosis. Eight (three lions, four tigers, and one leopard) animals were diagnosed with degenerative spinal disease. Clinical signs included progressively decreased activity, moderate to severe rear limb muscle atrophy, chronic intermittent rear limb paresis, and ataxia. The age at onset of clinical signs was 10-19 yr (median = 18 yr). Radiographic evaluation of the spinal column was useful in assessing the severity of spinal lesions, and results were correlated with necropsy findings. Lesions were frequently multifocal, included intervertebral disc mineralization or herniation with collapsed intervertebral disc spaces, and were most common in the lumbar area but also involved cervical and thoracic vertebrae. Marked spondylosis was present in the cats with intervertebral disc disease, presumably subsequent to vertebral instability. Six of the animals' spinal cords were examined histologically, and five had acute or chronic damage to the spinal cord secondary to disc protrusion. Spinal disease should be suspected in geriatric large felids with decreased appetite or activity. Radiographic evaluation of the spinal column is the most useful method to assess the type and severity of spinal lesions.

Evaluation of the health risks to garment workers in the city of Xambrê-PR, Brazil.

PubMed

Sant'Ana, Marco Antônio; Kovalechen, Fabrício

2012-01-01

This study evaluated the risks for cardiovascular disease and the life habits of garment industry workers in northwestern Paraná state, Brazil. The following parameters were assessed: body composition, cardiorespiratory fitness, eating habits and physical activities by garment industry workers. Cardiovascular risk was observed in some of the studied subjects, in the form of high BMI and reduced maximal oxygen uptake. The development of a workplace quality-of-life program is suggested, aiming to stimulate the development of physical activities to improve the cardiovascular conditioning of workers.

Evaluation and treatment of biking and running injuries.

PubMed

Oser, Sean M; Oser, Tamara K; Silvis, Matthew L

2013-12-01

Exercise is universally recognized as a key feature for maintaining good health. Likewise, lack of physical activity is a major risk factor for chronic disease and disability, an especially important fact considering our rapidly aging population. Biking and running are frequently recommended as forms of exercise. As more individuals participate in running-related and cycling-related activities, physicians must be increasingly aware of the common injuries encountered in these pursuits. This review focuses on the evaluation and management of common running-related and cycling-related injuries. Copyright © 2013 Elsevier Inc. All rights reserved.

A model for ubiquitous care of noncommunicable diseases.

PubMed

Vianna, Henrique Damasceno; Barbosa, Jorge Luis Victória

2014-09-01

The ubiquitous computing, or ubicomp, is a promising technology to help chronic diseases patients managing activities, offering support to them anytime, anywhere. Hence, ubicomp can aid community and health organizations to continuously communicate with patients and to offer useful resources for their self-management activities. Communication is prioritized in works of ubiquitous health for noncommunicable diseases care, but the management of resources is not commonly employed. We propose the UDuctor, a model for ubiquitous care of noncommunicable diseases. UDuctor focuses the resources offering, without losing self-management and communication supports. We implemented a system and applied it in two practical experiments. First, ten chronic patients tried the system and filled out a questionnaire based on the technology acceptance model. After this initial evaluation, an alpha test was done. The system was used daily for one month and a half by a chronic patient. The results were encouraging and show potential for implementing UDuctor in real-life situations.

Is Phosphoproteomics Ready for Clinical Research?

PubMed Central

Iliuk, Anton B.; Tao, W. Andy

2012-01-01

Background For many diseases such as cancer where phosphorylation-dependent signaling is the foundation of disease onset and progression, single-gene testing and genomic profiling alone are not sufficient in providing most critical information. The reason for this is that in these activated pathways the signaling changes and drug resistance are often not directly correlated with changes in protein expression levels. In order to obtain the essential information needed to evaluate pathway activation or the effects of certain drugs and therapies on the molecular level, the analysis of changes in protein phosphorylation is critical. Methods Existing approaches do not differentiate clinical disease subtypes on the protein and signaling pathway level, and therefore hamper the predictive management of the disease and the selection of therapeutic targets. Conclusions The mini-review examines the impact of emerging systems biology tools and the possibility of applying phosphoproteomics to clinical research. PMID:23159844

Pharmacophoric characteristics of dengue virus NS2B/NS3pro inhibitors: a systematic review of the most promising compounds.

PubMed

Leonel, Camyla Alves; Lima, William Gustavo; Dos Santos, Michelli; Ferraz, Ariane Coelho; Taranto, Alex Gutterres; de Magalhães, José Carlos; Dos Santos, Luciana Lara; Ferreira, Jaqueline Maria Siqueira

2018-03-01

Dengue virus (DENV) infection can lead to a wide range of clinical manifestations, including fatal hemorrhagic complications. There is a need to find effective pharmacotherapies to treat this disease due to the lack of specific immunotherapies and antiviral drugs. That said, the DENV NS2B/NS3pro protease complex is essential in both the viral multiplication cycle and in disease pathogenesis, and is considered a promising target for new antiviral therapies. Here, we performed a systematic review to evaluate the pharmacophoric characteristics of promising compounds against NS2B/NS3pro reported in the past 10 years. Online searches in the PUBMED/MEDLINE and SCOPUS databases resulted in 165 articles. Eight studies, which evaluated 3,384,268 molecules exhibiting protease inhibition activity, were included in this review. These studies evaluated anti-dengue activity in vitro and the IC 50 and EC 50 values were provided. Most compounds exhibited non-competitive inhibition. Cytotoxicity was evaluated in BHK-21, Vero, and LLC-MK2 cells, and the CC 50 values obtained ranged from < 1.0 to 780.5 µM. Several groups were associated with biological activity against dengue, including nitro, catechol, halogen and ammonium quaternaries. Thus, these groups seem to be potential pharmacophores that can be further investigated to treat dengue infections.

Role of physical activity in the management and assessment of rheumatoid arthritis patients.

PubMed

Hernández-Hernández, María Vanesa; Díaz-González, Federico

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting diarthrodial joints, in which patients tend to perform less physical activity (PA) than recommended. This review focuses on the existing evidence about the relationship of PA and RA, specifically how the former influences joint inflammation, disability, quality of life and pain in RA patients, and also how disease activity potentially impacts PA in these patients. A literature search of EMBASE and MEDLINE databases from January 2000 to January 2015. The evidence indicating that PA in RA patients is safe and the benefits from regularly performing, both aerobic and resistance exercises, in these patients include improvement in: quality of life, functionality, pain and number of swollen joints. Interestingly, recent studies suggest that changes in disease activity in RA patients inversely correlate with variations in PA, as assessed by accelerometry. The regular monitoring of PA in RA patients might facilitate a more objective evaluation of variations in disease activity, helping physicians to make general and therapeutic recommendations that will improve both the health status and the joint functionality of these patients. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Verbal and visual memory in patients with early Parkinson's disease: effect of levodopa.

PubMed

Singh, Sumit; Behari, Madhuri

2006-03-01

The effect of initiation of levodopa therapy on the memory functions in patients with Parkinson's disease remains poorly understood. To evaluate the effect of initiation of levodopa therapy on memory, in patients with early Parkinson's disease. Prospective case control study. Seventeen patients with early Parkinson's disease were evaluated for verbal memory using Rey's auditory verbal learning test, and visual memory using the Benton's visual retention test and Form sequence learning test. UPDRS scores, Hoehn and Yahr's Staging and Schwab and England scores of Activities of daily living. Hamilton's depression rating scale and MMSE were also evaluated. Six controls were also evaluated according to similar study protocol. Levodopa was then prescribed to the cases. Same tests were repeated on all the subjects after 12 weeks. The mean age of the patients was 59.8 (+ 12.9 yrs); mean disease duration of 3.26 (+ 2.06 yrs). The mean UPDRS scores of patients were 36.52 (+ 15.84). Controls were of a similar age and sex distribution. A statistically significant improvement in the scores on the UPDRS, Hamilton's depression scale, Schwab and England scale, and a statistically significant deterioration in the scores of visual memory was observed in patients with PD after starting levodopa, as compared to their baseline scores. There was no correlation between degree of deterioration and the dose of levodopa. Initiation of levodopa therapy in patients with early and stable Parkinson's disease is associated with deterioration in visual memory functions, with relative preservation of the verbal memory.

Evaluation of antibacterial, antioxidant and GC-MS analysis of ethanolic seed extract of Myristica dactyloides

NASA Astrophysics Data System (ADS)

Bhavani, R.; Vijayalakshmi, R.; Venkat Kumar, S.; Rajeshkumar, S.

2017-11-01

In this present investigation we analysed the antimicrobial and antioxidant activities of ethanol extract of Myristica dactyloides. The antimicrobial activity of the ethanol extract was evaluated by the agar well diffusion method against of E. coli, Klebsiella pneumonia, Streptococcus sp, and Staphylococcus aureus at different concentrations. The antibacterial activity showed the result in a dose-dependent manner. The free radical scavenging was evaluated against DPPH, hydroxyl, and nitric oxide radicals. In DPPH, hydroxyl and nitric oxide scavenging assay showed the IC 50 value of the extract was found to be 20 μg/ml, 48.25 and 30 μg/ml, respectively. The plant can be considered as promising antioxidant properties with high potential value for drug development for various diseases.

Design, synthesis and biological evaluation of LX2343 derivatives as neuroprotective agents for the treatment of Alzheimer's disease.

PubMed

Sun, Guanglong; Wang, Junwei; Guo, Xiaodan; Lei, Min; Zhang, Yinan; Wang, Xiachang; Shen, Xu; Hu, Lihong

2018-02-10

A series of LX2343 derivatives were designed, synthesized and evaluated as neuroprotective agents for Alzheimer's disease (AD) in vitro. Most of the compounds displayed potent neuroprotective activities. Especially for compound A6, exhibited a remarkable EC 50 value of 0.22 μM. Further investigation demonstrated that compound A6 can significantly reduce Aβ production and increase Aβ clearance, and alleviate Tau hyperphosphorylation. Most importantly, compound A6 could ameliorate learning and memory impairments in APP/PS1 transgenic mice. The present study evidently showed that compound A6 is a potent neuroprotective agent and might serve as a promising lead candidate for the treatment of Alzheimer's disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Physical activity, sedentary behavior, and vitamin D metabolites.

PubMed

Hibler, Elizabeth A; Sardo Molmenti, Christine L; Dai, Qi; Kohler, Lindsay N; Warren Anderson, Shaneda; Jurutka, Peter W; Jacobs, Elizabeth T

2016-02-01

Physical activity is associated with circulating 25-hydroxyvitamin D (25(OH)D). However, the influence of activity and/or sedentary behavior on the biologically active, seco-steroid hormone 1α,25-dihydroxyvitamin D (1,25(OH)2D) is unknown. We conducted a cross-sectional analysis among ursodeoxycholic acid (UDCA) randomized trial participants (n=876) to evaluate associations between physical activity, sedentary behavior, and circulating vitamin D metabolite concentrations. Continuous vitamin D metabolite measurements and clinical thresholds were evaluated using multiple linear and logistic regression models, mutually adjusted for either 1,25(OH)2D or 25(OH)D and additional confounding factors. A statistically significant linear association between 1,25(OH)2D and moderate-vigorous physical activity per week was strongest among women (β (95% CI): 3.10 (1.51-6.35)) versus men (β (95% CI): 1.35 (0.79-2.29)) in the highest tertile of activity compared to the lowest (p-interaction=0.003). Furthermore, 25(OH)D was 1.54ng/ml (95% CI 1.09-1.98) higher per hour increase in moderate-vigorous activity (p=0.001) and odds of sufficient 25(OH)D status was higher among physically active participants (p=0.001). Sedentary behavior was not significantly associated with either metabolite in linear regression models, nor was a statistically significant interaction by sex identified. The current study identified novel associations between physical activity and serum 1,25(OH)2D levels, adjusted for 25(OH)D concentrations. These results identify the biologically active form of vitamin D as a potential physiologic mechanism related to observed population-level associations between moderate-vigorous physical activity with bone health and chronic disease risk. However, future longitudinal studies are needed to further evaluate the role of physical activity and vitamin D metabolites in chronic disease prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

Do whole body vibration exercises affect lower limbs neuromuscular activity in populations with a medical condition? A systematic review.

PubMed

Dionello, Carla Fontoura; de Souza, Patrícia Lopes; Sá-Caputo, Danubia; Morel, Danielle Soares; Moreira-Marconi, Eloá; Paineiras-Domingos, Laisa Liane; Frederico, Eric Heleno Freire Ferreira; Guedes-Aguiar, Eliane; Paiva, Patricia de Castro; Taiar, Redha; Chiementin, Xavier; Marín, Pedro J; Bernardo-Filho, Mario

2017-01-01

The use of surface electromyography (sEMG) to evaluate muscle activation when executing whole body vibration exercises (WBVE) in studies provide neuromuscular findings, in healthy and diseased populations. Perform a systematic review of the effects of WBVE by sEMG of lower limbs in non-healthy populations. The search using the defined keywords was performed in PubMed, PEDRo and EMBASE databases by three independent researchers. Applying the PRISMA statement several studies were selected according to eligibility criteria and organized for the review. Full papers were included if they described effects of WBVE for the treatment of illnesses, evaluated by sEMG of lower limbs independently on the year of the publication; in comparison or associated with other treatment and evaluation techniques. Seven publications were selected; two in spinal cord injury patients, one in Friedreich's ataxia patients, three in stroke patients and one study in breast cancer survivors. Reported effects of WBV in were muscle activation by sEMG and also on strength, blood flow and exercise resistance; even in paretic limbs. By the use of sEMG it was verified that WBVE elicits muscle activation in diseased population. These results may lead to the definition of exercise protocols to maintain or increase muscular activation. However, due to the heterogeneity of methods among studies, there is currently no consensus on the sEMG signal processing. These strategies might also induce effects on muscle strength, balance and flexibility in these and other illnesses.

Physical activity level and associated factors among civil servants in Xi'an, China.

PubMed

Sun, Lijun; Jiang, Xun; Zhao, Xin; Zhang, Yuhai; Xu, Yongyong; Shang, Lei

2016-08-01

This study investigated physical activity levels and associated factors among civil servants in Xi'an, China, to provide reference data for the implementation of health improvement strategies among civil servants. A cross-section study. A random sample of 1000 civil servants aged 18-60 years and employed by the Xi'an civic government was assessed by using the Chinese version of the International Physical Activity Questionnaire. Associations between physical activity and sociodemographic characteristics, family history of chronic disease, and existing disease were evaluated by the Mann-Whitney U-test, Kruskal-Wallis H-test, and binary logistic regression. The response rate was 92.4%. The median physical activity score was 2227 metabolic equivalents of task (MET) minutes per week (interquartile range [IQR]: 1308-3802METmin/week). Among the 924 participants, 7.4% did not meet minimum recommendations for physical activity, 57.3% had moderate activity levels, and 35.4% had high activity levels. Participants spent most of their time on occupational activities (median: 869METmin/week, IQR: 228-1953METmin/week). Female sex (odds ratio [OR]:0.40, 95% confidence interval [CI]:0.29-0.55), age≥51 years (OR: 0.45, 95%CI: 0.27-0.75), and family history of chronic disease (OR: 0.67, 95%CI: 0.48-0.94) were associated with significantly lower odds of a high activity level. Most civil servants in Xi'an, China, have moderate activity levels. Some have high activity levels, but few engage in vigorous-intensity physical activity. Interventions to encourage a high level of physical activity are needed, especially for women, older civil servants, and those with family histories of chronic disease. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

A systematic review of the evidence for Canada's Physical Activity Guidelines for Adults

PubMed Central

2010-01-01

This systematic review examines critically the scientific basis for Canada's Physical Activity Guide for Healthy Active Living for adults. Particular reference is given to the dose-response relationship between physical activity and premature all-cause mortality and seven chronic diseases (cardiovascular disease, stroke, hypertension, colon cancer, breast cancer, type 2 diabetes (diabetes mellitus) and osteoporosis). The strength of the relationship between physical activity and specific health outcomes is evaluated critically. Literature was obtained through searching electronic databases (e.g., MEDLINE, EMBASE), cross-referencing, and through the authors' knowledge of the area. For inclusion in our systematic review articles must have at least 3 levels of physical activity and the concomitant risk for each chronic disease. The quality of included studies was appraised using a modified Downs and Black tool. Through this search we identified a total of 254 articles that met the eligibility criteria related to premature all-cause mortality (N = 70), cardiovascular disease (N = 49), stroke (N = 25), hypertension (N = 12), colon cancer (N = 33), breast cancer (N = 43), type 2 diabetes (N = 20), and osteoporosis (N = 2). Overall, the current literature supports clearly the dose-response relationship between physical activity and the seven chronic conditions identified. Moreover, higher levels of physical activity reduce the risk for premature all-cause mortality. The current Canadian guidelines appear to be appropriate to reduce the risk for the seven chronic conditions identified above and all-cause mortality. PMID:20459783

Fibromyalgia in patients with other rheumatic diseases: prevalence and relationship with disease activity.

PubMed

Haliloglu, Sema; Carlioglu, Ayse; Akdeniz, Derya; Karaaslan, Yasar; Kosar, Ali

2014-09-01

Fibromyalgia (FM) is a syndrome characterized by chronic widespread pain and the presence of specific tender points. The prevalence of FM has been estimated at 2-7 % of the general global population. The presence of FM in several rheumatic diseases with a structural pathology has been reported as 11-30 %. The objectives of this study were to determine the prevalence of FM and to evaluate the possible relationship between FM existence and disease activity among rheumatic diseases. The study group included 835 patients--197 rheumatoid arthritis (RA), 67 systemic lupus erythematosus (SLE), 119 ankylosing spondylitis (AS), 238 osteoarthritis (OA), 14 familial Mediterranean fever (FMF), 53 Behçet's disease (BD), 71 gout, 25 Sjögren's syndrome (SS), 20 vasculitis, 29 polymyalgia rheumatica (PMR), and two polymyositis (PM)--with or without FM. Recorded information included age, gender, laboratory parameters, presence of fatigue, and disease activity indexes. The prevalence of FM in patients with rheumatologic diseases was found to be 6.6 % for RA, 13.4 % for SLE, 12.6 % for AS, 10.1 % for OA, 5.7 % for BD, 7.1 % for FMF, 12 % for SS, 25 % for vasculitis, 1.4 % for gout, and 6.9 % for PMR. One out of two patients with PM was diagnosed with FM. Some rheumatologic cases (AS, OA) with FM were observed mostly in female patients (p = 0.000). Also, there were significant correlations between disease activity indexes and Fibromyalgia Impact Questionnaire scores for most rheumatologic patients (RA, AS, OA, and BD) (p < 0.05; respectively, r = 0.6, 0.95, 0.887, and 1). Concomitant FM is a common clinical problem in rheumatologic diseases, and its recognition is important for the optimal management of these diseases. Increased pain, physical limitations, and fatigue may be interpreted as increased activity of these diseases, and a common treatment option is the prescription of higher doses of biologic agents or corticosteroids. Considerations of the FM component in the management of rheumatologic diseases increase the likelihood of the success of the treatment.

Soluble CD163 is increased in patients with acute pancreatitis independent of disease severity.

PubMed

Karrasch, Thomas; Brünnler, Tanja; Hamer, Okka W; Schmid, Karin; Voelk, Markus; Herfarth, Hans; Buechler, Christa

2015-10-01

Macrophages are crucially involved in the pathophysiology of acute pancreatitis. Soluble CD163 (sCD163) is specifically released from macrophages and systemic levels are increased in inflammatory diseases. Here, sCD163 was measured in serum of 50 patients with acute pancreatitis to find out possible associations with disease activity. Admission levels of systemic sCD163 were nearly three-fold higher in patients with acute pancreatitis compared to controls. In patients sCD163 did not correlate with C-reactive protein and leukocyte count as established markers of inflammation. Levels were not associated with disease severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age, and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis score. Soluble CD163 was not related to complications of acute pancreatitis. These data show that serum sCD163 is increased in acute pancreatitis indicating activation of macrophages but is not associated with disease severity and outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Black leaf streak disease affects starch metabolism in banana fruit.

PubMed

Saraiva, Lorenzo de Amorim; Castelan, Florence Polegato; Shitakubo, Renata; Hassimotto, Neuza Mariko Aymoto; Purgatto, Eduardo; Chillet, Marc; Cordenunsi, Beatriz Rosana

2013-06-12

Black leaf streak disease (BLSD), also known as black sigatoka, represents the main foliar disease in Brazilian banana plantations. In addition to photosynthetic leaf area losses and yield losses, this disease causes an alteration in the pre- and postharvest behavior of the fruit. The aim of this work was to investigate the starch metabolism of fruits during fruit ripening from plants infected with BLSD by evaluating carbohydrate content (i.e., starch, soluble sugars, oligosaccharides, amylose), phenolic compound content, phytohormones, enzymatic activities (i.e., starch phosphorylases, α- and β-amylase), and starch granules. The results indicated that the starch metabolism in banana fruit ripening is affected by BLSD infection. Fruit from infested plots contained unusual amounts of soluble sugars in the green stage and smaller starch granules and showed a different pattern of superficial degradation. Enzymatic activities linked to starch degradation were also altered by the disease. Moreover, the levels of indole-acetic acid and phenolic compounds indicated an advanced fruit physiological age for fruits from infested plots.

Positron emission tomography/computed tomography imaging and rheumatoid arthritis.

PubMed

Wang, Shi-Cun; Xie, Qiang; Lv, Wei-Fu

2014-03-01

Rheumatoid arthritis (RA) is a phenotypically heterogeneous, chronic, destructive inflammatory disease of the synovial joints. A number of imaging tools are currently available for evaluation of inflammatory conditions. By targeting the upgraded glucose uptake of infiltrating granulocytes and tissue macrophages, positron emission tomography/computed tomography with fluorine-18 fluorodeoxyglucose ((18) F-FDG PET/CT) is available to delineate inflammation with high sensitivity. Recently, several studies have indicated that FDG uptake in affected joints reflects the disease activity of RA. In addition, usage of FDG PET for the sensitive detection and monitoring of the response to treatment has been reported. Combined FDG PET/CT enables the detailed assessment of disease in large joints throughout the whole body. These unique capabilities of FDG PET/CT imaging are also able to detect RA-complicated diseases. Therefore, PET/CT has become an excellent ancillary tool to assess disease activity and prognosis in RA. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Targeting monoamine oxidases with multipotent ligands: an emerging strategy in the search of new drugs against neurodegenerative diseases.

PubMed

Pisani, L; Catto, M; Leonetti, F; Nicolotti, O; Stefanachi, A; Campagna, F; Carotti, A

2011-01-01

The socioeconomic burden of multi-factorial pathologies, such as neurodegenerative diseases (NDs), is enormous worldwide. Unfortunately, no proven disease-modifying therapy is available yet and in most cases (e.g., Alzheimer's and Parkinson's disease) the approved drugs exert only palliative and symptomatic effects. Nowadays, an emerging strategy for the discovery of disease-modifying drugs is based on the multi-target directed ligand (MTDL) design, an innovative shift from the traditional approach one-drug-one-target to the more ambitious one-drug-more-targets goal. Herein, we review the discovery strategy, the mechanism of action and the biopharmacological evaluation of multipotent ligands exhibiting monoamine oxidase (MAO) inhibition as the core activity with a potential for the treatment of NDs. In particular, MAO inhibitors exhibiting additional acetylcholinesterase (AChE) or nitric oxide synthase (NOS) inhibition, or ion chelation/antioxidant-radical scavenging/anti-inflammatory/A2A receptor antagonist/APP processing modulating activities have been thoroughly examined.

Targeting neuronal MAPK14/p38α activity to modulate autophagy in the Alzheimer disease brain.

PubMed

Alam, John; Scheper, Wiep

2016-12-01

Dysregulated autophagic-lysosomal degradation of proteins has been linked to the most common genetic defect in familial Alzheimer disease, and has been correlated with disease progression in both human disease and in animal models. Recently, it was demonstrated that the expression of MAPK14/p38α protein is upregulated in the brain of APP-PS1 transgenic Alzheimer mouse and further that genetic deficiency of Mapk14 in the APP-PS1 mouse stimulates macroautophagy/autophagy, which then leads to reduced amyloid pathology via increasing autophagic-lysosomal degradation of BACE1. The findings resolve at least in the context of the APP-PS1 mouse, prior conflicting in vitro observations that have implicated MAPK14 in autophagic processes, and indicate that inhibition of MAPK14 enzyme activity has potential as a therapeutic approach to mitigate a critical physiological defect within neurons of the Alzheimer disease brain. Moreover, the findings suggest that biomarkers of BACE1 activity could be utilized to evaluate the effects of MAPK14 inhibition and other autophagy-inducing therapeutic approaches in human clinical studies, thereby potentially facilitating the clinical development of such agents.

Functional mechanism of neuroprotection by inhibitors of type B monoamine oxidase in Parkinson's disease.

PubMed

Naoi, Makoto; Maruyama, Wakako

2009-08-01

Neuroprotective therapy has been proposed for age-related neurodegenerative disorders, including Parkinson's disease. Inhibitors of type B monoamine oxidase (MAOB-Is), rasagiline and (-)deprenyl, are the most promising candidate neuroprotective drugs. Clinical trials of rasagiline in patients with Parkinson's disease suggest that rasagiline may have some disease-modifying effects. Results using animal and cellular models have proved that the MAOB-Is protect neurons by the intervention of 'intrinsic' mitochondrial apoptotic cascade and the induction of prosurvival antiapoptotic Bcl-2 and neurotrophic factors. Rasagiline-related MAOB-Is prevent mitochondrial permeability transition induced by various insults and activation of subsequent apoptotic cascades: cytochrome c release, casapase activation, and condensation and fragmentation of nuclear DNA. MAOB-Is increase transcription of prosurvival genes through activating the nuclear transcription factor-(NF) system. Rasagiline increases the protein and mRNA levels of GDNF in dopaminergic SH-SY5Y cells, whereas (-)deprenyl increases those of BDNF. Systemic administration of (-)deprenyl and rasagiline increases these neurotrophic factors in the cerebrospinal fluid from patients with Parkinson's disease and nonhuman primates. This review presents recent advances in our understanding of the neuroprotection offered by MAOB-Is and possible evaluation of neuroprotective efficacy in clinical samples is discussed.

Targeting neuronal MAPK14/p38α activity to modulate autophagy in the Alzheimer disease brain

PubMed Central

Alam, John; Scheper, Wiep

2016-01-01

ABSTRACT Dysregulated autophagic-lysosomal degradation of proteins has been linked to the most common genetic defect in familial Alzheimer disease, and has been correlated with disease progression in both human disease and in animal models. Recently, it was demonstrated that the expression of MAPK14/p38α protein is upregulated in the brain of APP-PS1 transgenic Alzheimer mouse and further that genetic deficiency of Mapk14 in the APP-PS1 mouse stimulates macroautophagy/autophagy, which then leads to reduced amyloid pathology via increasing autophagic-lysosomal degradation of BACE1. The findings resolve at least in the context of the APP-PS1 mouse, prior conflicting in vitro observations that have implicated MAPK14 in autophagic processes, and indicate that inhibition of MAPK14 enzyme activity has potential as a therapeutic approach to mitigate a critical physiological defect within neurons of the Alzheimer disease brain. Moreover, the findings suggest that biomarkers of BACE1 activity could be utilized to evaluate the effects of MAPK14 inhibition and other autophagy-inducing therapeutic approaches in human clinical studies, thereby potentially facilitating the clinical development of such agents. PMID:27715387

Evaluation of therapeutic effect of low dose naltrexone in experimentally-induced Crohn's disease in rats.

PubMed

Tawfik, Dina Ibrahim; Osman, Afaf Sayed; Tolba, Hedayat Mahmoud; Khattab, Aida; Abdel-Salam, Lubna O; Kamel, Mahmoud M

2016-10-01

Crohn's disease is a relapsing inflammatory condition afflicting the digestive tract. Drugs used for treatment of Crohn's disease may be associated with serious side effects. Endogenous opioid peptides modulate inflammatory cytokine production. Opioid antagonists have been shown to play a role in healing and repair of tissues. This work was designed to detect the possible beneficial effects of opioid antagonist naltrexone in indomethacin-induced Crohn's disease in rats. Enteritis was induced in male albino rats by two subcutaneous injection of indomethacin in a dose of 7.5mg/kg 24h apart started on day one. Salfasalazine, naltrexone and their combination were administered orally from day one of induction of enteritis to day 10. Disease activity index, serum levels of C-reactive protein and tumor necrosis factor-α, macroscopic and microscopic pathological scores and in vitro motility studies were evaluated. Induction of enteritis resulted in significant increase of disease activity index, significant elevation of serum levels of C-reactive protein and tumor necrosis factor-α, significant deterioration of pathological scores and significant increase in the mean contractility response of the isolated ileal segments compared with normal untreated rats. Treatment with sulfasalazine, low dose of natrexone or their combination resulted in significant improvement of all measured parameters compared with enteritis group. The current finding could provide new interesting opportunity for developing new therapeutic approaches for treatment of Crohn's disease. Use of naltrexone, especially in small dose, has little side effects making it of interest for treatment of Crohn's disease. Also, it provides the possibility of reduced doses of other drugs if it is used as combined therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Medicinal plants combating against cancer--a green anticancer approach.

PubMed

Sultana, Sabira; Asif, Hafiz Muhammad; Nazar, Hafiz Muhammad Irfan; Akhtar, Naveed; Rehman, Jalil Ur; Rehman, Riaz Ur

2014-01-01

Cancer is the most deadly disease that causes the serious health problems, physical disabilities, mortalities, and morbidities around the world. It is the second leading cause of death all over the world. Although great advancement have been made in the treatment of cancer progression, still significant deficiencies and room for improvement remain. Chemotherapy produced a number of undesired and toxic side effects. Natural therapies, such as the use of plant-derived products in the treatment of cancer, may reduce adverse and toxic side effects. However, many plants exist that have shown very promising anticancer activities in vitro and in vivo but their active anticancer principle have yet to be evaluated. Combined efforts of botanist, pharmacologist and chemists are required to find new lead anticancer constituent to fight disease. This review will help researchers in the finding of new bioactive molecules as it will focus on various plants evaluated for anticancer properties in vitro and in vivo.

Design, synthesis and biological evaluation of novel 6H-benzo[c]chromen-6-one, and 7,8,9,10-tetrahydro-benzo[c]chromen-6-one derivatives as potential cholinesterase inhibitors.

PubMed

Gulcan, Hayrettin Ozan; Unlu, Serdar; Esiringu, Ilker; Ercetin, Tugba; Sahin, Yasemin; Oz, Demet; Sahin, Mustafa Fethi

2014-10-01

Hydroxylated 6H-benzo[c]chromen-6-one derivatives (i.e., urolithins) are the main bioavailable metabolites, and biomarkers of ellagitannins present in various nutrition. Although these dietaries, the sources of urolithins, are employed in folk medicine as cognitive enhancer in the treatment of Alzheimer's Disease, urolithins have negligible potential to inhibit acetylcholinesterase and butyrylcholinesterase enzymes, the validated targets of Alzheimer's Disease. Therefore, within this research, a series of 6H-benzo[c]chromen-6-one, and 7,8,9,10-tetrahydro-benzo[c]chromen-6-one derivatives has been designed, synthesized, and their biological activities were evaluated as potential acetylcholinesterase and butyrylcholinesterase inhibitors. The compounds synthesized exerted comparable activity in comparison to rivastigmine, galantamine, and donepezil both in in vitro and in vivo studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Safety and tolerability of low-dose naltrexone therapy in children with moderate to severe Crohn's disease: a pilot study.

PubMed

Smith, Jill P; Field, Douglas; Bingaman, Sandra I; Evans, Robert; Mauger, David T

2013-04-01

There is an unmet need for safe and effective medicines to treat children with Crohn's disease. Recently, investigations have shown an association between endogenous opioid peptides and inflammatory cells. The aims of this study were to evaluate the safety and tolerability of an opioid antagonist, naltrexone, in children with moderate to severe Crohn's disease. A pilot clinical trial was conducted in children with moderate to severe Crohn's disease. Fourteen subjects with a mean age of 12.3 years (range, 8 to 17 y) were enrolled. Children were randomized to placebo or naltrexone (0.1 mg/kg) orally for 8 weeks followed by open-labeled treatment with 8 additional weeks of naltrexone. Safety and toxicity were monitored by physical examinations and blood chemistries. Clinical activity was assessed by the Pediatric Crohn's Disease Activity Index (PCDAI) and Quality of life was monitored by the Impact III survey. Oral naltrexone was well tolerated without any serious adverse events in children with moderate to severe Crohn's disease. PCDAI scores significantly decreased from pretreatment values (34.2±3.3) with an 8-week course of naltrexone therapy (21.7±3.9) (P=0.005). Twenty-five percent of those treated with naltrexone were considered in remission (score ≤10) and 67% had improved with mild disease activity (decrease in PCDAI score by at least 10 points) at the end of the study. Systemic and social quality of life improved with naltrexone treatment (P=0.035). Naltrexone therapy seems safe with limited toxicity when given to children with Crohn's disease and may reduce disease activity.