A brief history of the Bioengineering Institute of California and the UC System-wide Symposia.

PubMed

Chien, Shu

2011-04-01

The plan to establish a Multicampus Research Unit (MRU) on Bioengineering in the University of California (UC) System started in August 1999. The cooperative efforts of the UC campuses led to the formal establishment of the Bioengineering Institute of California (BIC) in October 2003. Three years prior to the BIC establishment, the System-wide Annual Bioengineering Symposium was started at UC Davis. The Symposia were then hosted sequentially by UC Santa Barbara, UC Berkeley, UCSD, UC Santa Cruz, UC Irvine, UCSF, UCLA, and UC Riverside, with the completion of the first cycle of a decade in the newest campus of UC Merced in 2009. The second cycle began in 2010 with the Symposium returning again to UC Davis. Each campus hosted a wonderful Symposium, with the active participation of students and faculty from all campuses, with the motto of "Ten campuses united as one, learning and growing together." These Symposia have contributed significantly to the collaborative research and training of students and young scientists in bioengineering, as well as fruitful interactions with industry and government agencies, which have provided strong support for these valuable meetings. The BIC will endeavor to further enhance these efforts by fostering research collaborations and joint education and training activities, with the ultimate goal of advancing bioengineering for the improvement of human health and wellbeing.

Appendectomy does not decrease the risk of future colectomy in UC: results from a large cohort and meta-analysis.

PubMed

Parian, Alyssa; Limketkai, Berkeley; Koh, Joyce; Brant, Steven R; Bitton, Alain; Cho, Judy H; Duerr, Richard H; McGovern, Dermot P; Proctor, Deborah D; Regueiro, Miguel D; Rioux, John D; Schumm, Phil; Taylor, Kent D; Silverberg, Mark S; Steinhart, A Hillary; Hernaez, Ruben; Lazarev, Mark

2017-08-01

Early appendectomy is inversely associated with the development of UC. However, the impact of appendectomy on the clinical course of UC is controversial, generally favouring a milder disease course. We aim to describe the effect appendectomy has on the disease course of UC with focus on the timing of appendectomy in relation to UC diagnosis. Using the National Institute of Diabetes and Digestive and Kidney Diseases Inflammatory Bowel Disease Genetics Consortium database of patients with UC, the risk of colectomy was compared between patients who did and did not undergo appendectomy. In addition, we performed a meta-analysis of studies that examined the association between appendectomy and colectomy. 2980 patients with UC were initially included. 111 (4.4%) patients with UC had an appendectomy; of which 63 were performed prior to UC diagnosis and 48 after diagnosis. In multivariable analysis, appendectomy performed at any time was an independent risk factor for colectomy (OR 1.9, 95% CI 1.1 to 3.1), with appendectomy performed after UC diagnosis most strongly associated with colectomy (OR 2.2, 95% CI 1.1 to 4.5). An updated meta-analysis showed appendectomy performed either prior to or after UC diagnosis had no effect on colectomy rates. Appendectomy performed at any time in relation to UC diagnosis was not associated with a decrease in severity of disease. In fact, appendectomy after UC diagnosis may be associated with a higher risk of colectomy. These findings question the proposed use of appendectomy as treatment for UC. 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/.

High within-day variability of fecal calprotectin levels in patients with active ulcerative colitis: what is the best timing for stool sampling?

PubMed

Calafat, Margalida; Cabré, Eduard; Mañosa, Míriam; Lobatón, Triana; Marín, Laura; Domènech, Eugeni

2015-05-01

Fecal calprotectin (FC) is considered the best noninvasive way to assess disease activity in ulcerative colitis (UC). However, it is not known which is the more suitable moment for stool sampling in patients with increased stool frequency. The aims of this study were to assess the intraindividual variation of FC within day and to evaluate if the first bowel movement in the morning is the more suitable sample for FC measurement in patients with acute flares of UC. Patients admitted because of active UC were invited to collect samples from several bowel movements (including the first in the morning) during the same day providing their ordinal chronology. FC was measured by means of a quantitative rapid point-of-care test based on lateral flow assay immunochromatography. Eighteen patients were included for a total of 56 stool samples. Most patients had extensive UC and severe disease activity. Within-day FC values varied widely, and the median coefficient of variation was 40% (5%-114%) with a median range of variation of FC values of 3887 mg/kg (69-9946). The sample from the first stool in the morning obtained the highest individual FC within-day value in 33.3% of cases and the lowest in 38.9%. FC values widely vary between motions in patients with active UC. Stool sample collection from the first bowel movement in the morning does not ensure the highest or lowest within-day FC value. In patients with overt active UC, a single FC determination should not be used as the basis for therapeutic strategies.

Protease signaling through protease activated receptor 1 mediate nerve activation by mucosal supernatants from irritable bowel syndrome but not from ulcerative colitis patients

PubMed Central

Buhner, Sabine; Hahne, Hannes; Hartwig, Kerstin; Li, Qin; Vignali, Sheila; Ostertag, Daniela; Meng, Chen; Hörmannsperger, Gabriele; Braak, Breg; Pehl, Christian; Frieling, Thomas; Barbara, Giovanni; De Giorgio, Roberto; Demir, Ihsan Ekin; Ceyhan, Güralp Onur; Zeller, Florian; Boeckxstaens, Guy; Haller, Dirk; Kuster, Bernhard

2018-01-01

Background & aims The causes of gastrointestinal complaints in irritable bowel syndrome (IBS) remain poorly understood. Altered nerve function has emerged as an important pathogenic factor as IBS mucosal biopsy supernatants consistently activate enteric and sensory neurons. We investigated the neurally active molecular components of such supernatants from patients with IBS and quiescent ulcerative colitis (UC). Method Effects of supernatants from 7 healthy controls (HC), 20 IBS and 12 UC patients on human and guinea pig submucous neurons were studied with neuroimaging techniques. We identify differentially expressed proteins with proteome analysis. Results Nerve activation by IBS supernatants was prevented by the protease activated receptor 1 (PAR1) antagonist SCHE79797. UC supernatants also activated enteric neurons through protease dependent mechanisms but without PAR1 involvement. Proteome analysis of the supernatants identified 204 proteins, among them 17 proteases as differentially expressed between IBS, UC and HC. Of those the four proteases elastase 3a, chymotrypsin C, proteasome subunit type beta-2 and an unspecified isoform of complement C3 were significantly more abundant in IBS compared to HC and UC supernatants. Of eight proteases, which were upregulated in IBS, the combination of elastase 3a, cathepsin L and proteasome alpha subunit-4 showed the highest prediction accuracy of 98% to discriminate between IBS and HC groups. Elastase synergistically potentiated the effects of histamine and serotonin–the two other main neuroactive substances in the IBS supernatants. A serine protease inhibitor isolated from the probiotic Bifidobacterium longum NCC2705 (SERPINBL), known to inhibit elastase-like proteases, prevented nerve activation by IBS supernatants. Conclusion Proteases in IBS and UC supernatants were responsible for nerve activation. Our data demonstrate that proteases, particularly those signalling through neuronal PAR1, are biomarker candidates for

Delayed-release oral mesalamine 4.8 g/day (800-mg tablet) is effective for patients with moderately active ulcerative colitis.

PubMed

Sandborn, William J; Regula, Jaroslaw; Feagan, Brian G; Belousova, Elena; Jojic, Njegica; Lukas, Milan; Yacyshyn, Bruce; Krzeski, Piotr; Yeh, Chyon-Hwa; Messer, Christi A; Hanauer, Stephen B

2009-12-01

It is not clear what induction dose of mesalamine is optimal for treating patients with mildly and moderately active ulcerative colitis (UC). This study was conducted to determine the efficacy and safety of mesalamine 4.8 g/day compared with 2.4 g/day for the treatment of moderately active UC. A multicenter, randomized, double-blind, 6-week, active-control study (ASCEND III) was conducted to assess the noninferiority of delayed-release mesalamine 4.8 g/day (Asacol HD, 800-mg tablet; Procter & Gamble, Pharmaceuticals, Inc, Mason, Ohio) with 2.4 g/day (Asacol, 400-mg tablet; Procter & Gamble Pharmaceuticals, Inc) in 772 patients with moderately active UC. The primary endpoint was treatment success (overall improvement) at week 6, defined as improvement in the Physician's Global Assessment (based on clinical assessments of rectal bleeding, stool frequency, and sigmoidoscopy), with no worsening in any individual clinical assessment. The primary objective of noninferiority was met. Seventy percent (273 of 389) of patients who received 4.8 g/day of mesalamine achieved treatment success at week 6, compared with 66% (251 of 383) of patients receiving 2.4 g/day (95% confidence interval for 2.4 g/day minus 4.8 g/day, -11.2 to 1.9). In addition, 43% of patients who received 4.8 g/day mesalamine achieved clinical remission at week 6 compared with 35% of patients who received 2.4 g/day (P = .04). A therapeutic advantage for the 4.8 g/day dose was observed among patients previously treated with corticosteroids, oral mesalamines, rectal therapies, or multiple UC medications. Both regimens were well-tolerated with similar adverse events. Delayed-release mesalamine 4.8 g/day (800-mg tablet) is efficacious and well-tolerated in patients with moderately active UC.

UCS-PROMOVE: The engineer of the future

NASA Astrophysics Data System (ADS)

Villas-Boas, V.

2010-06-01

The Universidade de Caxias do Sul (UCS) elaborated the cooperative project called 'The engineer of the future', with the objective of promoting science and engineering among high school teachers and students. This project aims to improve the quality of the teaching and to increase the interest of students in technological areas, leading to a future career in engineering. The activities of this project were planned to give meaning and foundation to the teaching-learning process of science and for the application of theory in the solution of real problems, while articulating scientific, economic, environmental, social and political aspects and also to reinforce the important role of engineering in society. Amongst the activities to be offered to high school teachers and students are a specialisation course for teachers based upon new educational methodologies, workshops in different areas of science and technology, a programme entitled 'Encouraging girls in technology, science and engineering', science fairs and visits to the industries of the region. Activities with the engineering instructors of UCS are also being developed in order to help them to incorporate in their classes more effective pedagogical strategies for educating the engineer-to-be.

Development of a UC781 releasing polyethylene vinyl acetate vaginal ring.

PubMed

McConville, Christopher; Major, Ian; Friend, David R; Clark, Meredith R; Malcolm, R Karl

2012-12-01

UC781 is potent, hydrophobic, non-nucleotide reverse transcriptase inhibitor (NNRTI) against the human immunodeficiency virus (HIV). UC781 is currently being investigated for use as a potential HIV microbicide. A study in rhesus macaques demonstrated that a 100-mg UC781-loaded silicone elastomer vaginal ring released limited amounts of UC781 into the vaginal fluid and tissue after 28 days. The reason for this was due to the hydrophobic nature and limited aqueous solubility of UC781. This study describes the manufacture of UC781-loaded polyethylene vinyl acetate (PEVA) vaginal rings, which have an improved in vitro release rate of UC781 when compared to UC781-loaded silicone elastomer vaginal rings. The study demonstrates that the UC781 in the PEVA rings is mostly in its amorphous form due to the rings being manufactured above UC781's melting point. Furthermore, the rings do not show any signs of UC781 degradation, such as the presence of UC22.

Genetic characterization of the UCS and Kex1 loci of Pneumocystis jirovecii.

PubMed

Esteves, F; Tavares, A; Costa, M C; Gaspar, J; Antunes, F; Matos, O

2009-02-01

Nucleotide variation in the Pneumocystis jirovecii upstream conserved sequence (UCS) and kexin-like serine protease (Kex1) loci was studied in pulmonary specimens from Portuguese HIV-positive patients. DNA was extracted and used for specific molecular sequence analysis. The number of UCS tandem repeats detected in 13 successfully sequenced isolates ranged from three (9 isolates, 69%) to four (4 isolates, 31%). A novel tandem repeat pattern and two novel polymorphisms were detected in the UCS region. For the Kex1 gene, the wild-type (24 isolates, 86%) was the most frequent sequence detected among the 28 sequenced isolates. Nevertheless, a nonsynonymous (1 isolate, 3%) and three synonymous (3 isolates, 11%) polymorphisms were detected and are described here for the first time.

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.

Motivational counselling for physical activity in patients with coronary artery disease not participating in cardiac rehabilitation.

PubMed

Reid, Robert D; Morrin, Louise I; Higginson, Lyall A J; Wielgosz, Andreas; Blanchard, Chris; Beaton, Louise J; Nelson, Chantal; McDonnell, Lisa; Oldridge, Neil; Wells, George A; Pipe, Andrew L

2012-04-01

Many patients with coronary artery disease (CAD) fail to attend cardiac rehabilitation following acute coronary events because they lack motivation to exercise. Theory-based approaches to promote physical activity among non-participants in cardiac rehabilitation are required. A randomized trial comparing physical activity levels at baseline, 6, and 12 months between a motivational counselling (MC) intervention group and a usual care (UC) control group. One hundred and forty-one participants hospitalized with acute coronary syndromes not planning to attend cardiac rehabilitation were recruited at a single centre and randomized to either MC (n = 69) or UC (n = 72). The MC intervention, designed from an ecological perspective, included one face-to-face contact and eight telephone contacts with a trained physiotherapist over a 52-week period. The UC group received written information about starting a walking programme and brief physical activity advice from their attending cardiologist. Physical activity was measured by: 7-day physical activity recall interview; self-report questionnaire; and pedometer at baseline, 6, and 12 months after randomization. Latent growth curve analyses, which combined all three outcome measures into a single latent construct, showed that physical activity increased more over time in the MC versus the UC group (µ(add) = 0.69, p < 0.05). Patients with CAD not participating in cardiac rehabilitation receiving a theory-based motivational counselling intervention were more physically active at follow-up than those receiving usual care. This intervention may extend the reach of cardiac rehabilitation by increasing physical activity in those disinclined to participate in structured programmes.

Relationship and significance between anti-beta2-glycoprotein I antibodies and platelet activation state in patients with ulcerative colitis.

PubMed

Gao, Yan-Hang; Gao, Pu-Jun; Wang, Chun-Guang; Wang, Xiao-Cong; Piao, Yun-Feng

2008-02-07

To study the relationship between anti-beta2-glycoprotein I (abeta2GPI) antibodies and platelet activation state in patients with ulcerative colitis (UC) and its significance. Peripheral blood samples were collected from 56 UC patients (34 males and 22 females, aged 43.5 years, range 21-66 years), including 36 at active stage and 20 at remission stage, and 25 sex-and age-matched controls. The level of abeta2GPI was measured by ELISA. The platelet activation markers, platelet activation complex-I (PAC-I) and P-selectin (CD62P) were detected by flow cytometry. The A value for IgG abeta2GPI in the active UC group was 0.61 +/- 0.13, significantly higher than that in the remittent UC and control groups (0.50 +/- 0.13 and 0.22 +/- 0.14, P < 0.01). There was a significant difference between the two groups (P < 0.01). The A value for IgM abeta2GPI in the active and remittent UC groups was 0.43 +/- 0.13 and 0.38 +/- 0.12, significantly higher than that in the control group (0.20 +/- 0.12, P < 0.01). However, there was no significant difference between the two groups (P > 0.05). The PAC-I positive rate for the active and remittent UC groups was 30.6% +/- 7.6% and 19.6% +/- 7.8% respectively, significantly higher than that for the control group (6.3% +/- 1.7%, P < 0.01). There was a significant difference between the two groups (P < 0.01). The CD62P positive rate for the active and remittent UC groups was 45.0% +/- 8.8% and 31.9% +/- 7.8% respectively, significantly higher than that for the control group (9.2% +/- 2.7%, P < 0.01). There was a significant difference between the two groups (P < 0.01). In the active UC group, the more severe the state of illness was, the higher the A value for IgG abeta2GPI was, and the positive rate for PAC-I and CD62P was positively correlated with the state of illness (Fabeta2GPI = 3.679, P < 0.05; FPAC-I (%) = 5.346, P < 0.01; and FCD62P (%) = 5. 418, P < 0.01). Meanwhile, in the same state of illness, the A value for IgG abeta2GPI was

Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs.

PubMed

Deparle, L A; Gupta, R C; Canerdy, T D; Goad, J T; D'Altilio, M; Bagchi, M; Bagchi, D

2005-08-01

DeParle L. A., Gupta R. C., Canerdy T. D., Goad J. T., D'Altilio M., Bagchi M., Bagchi D. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs. J. vet. Pharmacol. Therap.28, 385-390. In large breed dogs, arthritis is very common because of obesity, injury, aging, immune disorder, or genetic predispositions. This study was therefore undertaken to evaluate clinical efficacy and safety of undenatured type-II collagen (UC-II) in obese-arthritic dogs. Fifteen dogs in three groups received either no UC-II (Group I) or UC-II with 1 mg/day (Group II) or 10 mg/day (Group III) for 90 days. Lameness and pain were measured on a weekly basis for 120 days (90 days treatment plus 30 days post-treatment). Blood samples were assayed for creatinine and blood urea nitrogen (markers of renal injury); and alanine aminotransferase and aspartate aminotransferase (evidence of hepatic injury). Dogs receiving 1 mg or 10 mg UC-II/day for 90 days showed significant declines in overall pain and pain during limb manipulation and lameness after physical exertion, with 10 mg showed greater improvement. At either dose of UC-II, no adverse effects were noted and no significant changes were noted in serum chemistry, suggesting that UC-II was well tolerated. In addition, dogs receiving UC-II for 90 days showed increased physical activity level. Following UC-II withdrawal for a period of 30 days, all dogs experienced a relapse of overall pain, exercise-associated lameness, and pain upon limb manipulation. These results suggest that daily treatment of arthritic dogs with UC-II ameliorates signs and symptoms of arthritis, and UC-II is well tolerated as no adverse effects were noted.

IBS-like symptoms in patients with ulcerative colitis

PubMed Central

Gracie, David J; Ford, Alexander C

2015-01-01

Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are chronic gastrointestinal disorders that, until recently, have been considered dichotomous conditions falling on either side of a functional-organic divide. However, persistent gastrointestinal symptoms, akin to those of IBS, are observed in up to one in three patients with quiescent UC. Whether these lower gastrointestinal symptoms are secondary to coexistent IBS or occult UC disease activity is uncertain, but when objective evidence of disease activity is lacking, escalation of conventional pharmacotherapy in such patients is often ineffective. The etiologies of both UC and IBS remain unclear, but dysregulation of the enteric nervous system, an altered microbiome, low-grade mucosal inflammation, and activation of the brain–gut axis is common to both; this suggests that some overlap between the two conditions is plausible. How best to investigate and manage IBS-type symptoms in UC patients remains unclear. Studies that have assessed patients with UC who meet criteria for IBS for subclinical inflammation have been conflicting in their results. Although evidence-based treatments for IBS exist, their efficacy in UC patients reporting these types of symptoms remains unclear. Given the disturbances in gut microbiota in UC, and the possible role of the brain–gut axis in the generation of such symptoms, treatments such as probiotics, fecal transfer, antidepressants, or psychological therapies would seem logical approaches to use in this group of patients. However, there are only limited data for all of these therapies; this suggests that randomized controlled trials to investigate their efficacy in this setting may be warranted. PMID:25733921

IBS-like symptoms in patients with ulcerative colitis.

PubMed

Gracie, David J; Ford, Alexander C

2015-01-01

Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are chronic gastrointestinal disorders that, until recently, have been considered dichotomous conditions falling on either side of a functional-organic divide. However, persistent gastrointestinal symptoms, akin to those of IBS, are observed in up to one in three patients with quiescent UC. Whether these lower gastrointestinal symptoms are secondary to coexistent IBS or occult UC disease activity is uncertain, but when objective evidence of disease activity is lacking, escalation of conventional pharmacotherapy in such patients is often ineffective. The etiologies of both UC and IBS remain unclear, but dysregulation of the enteric nervous system, an altered microbiome, low-grade mucosal inflammation, and activation of the brain-gut axis is common to both; this suggests that some overlap between the two conditions is plausible. How best to investigate and manage IBS-type symptoms in UC patients remains unclear. Studies that have assessed patients with UC who meet criteria for IBS for subclinical inflammation have been conflicting in their results. Although evidence-based treatments for IBS exist, their efficacy in UC patients reporting these types of symptoms remains unclear. Given the disturbances in gut microbiota in UC, and the possible role of the brain-gut axis in the generation of such symptoms, treatments such as probiotics, fecal transfer, antidepressants, or psychological therapies would seem logical approaches to use in this group of patients. However, there are only limited data for all of these therapies; this suggests that randomized controlled trials to investigate their efficacy in this setting may be warranted.

Differential effects of α4β7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo.

PubMed

Fischer, Anika; Zundler, Sebastian; Atreya, Raja; Rath, Timo; Voskens, Caroline; Hirschmann, Simon; López-Posadas, Rocío; Watson, Alastair; Becker, Christoph; Schuler, Gerold; Neufert, Clemens; Atreya, Imke; Neurath, Markus F

2016-10-01

Gut homing of lymphocytes via adhesion molecules has recently emerged as new target for therapy in IBDs. We aimed to analyse the in vivo homing of effector (Teff) and regulatory (Treg) T cells to the inflamed gut via α4β7 and G protein receptor GPR15. We assessed the expression of homing receptors on T cells in peripheral blood and inflamed mucosa. We studied the migration pattern and homing of Teff and Treg cells to the inflamed gut using intravital confocal microscopy and FACS in a humanised mouse model in dextran sodium sulfate-treated NSG (NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ) mice. Expression of GPR15 and α4β7 was significantly increased on Treg rather than Teff cells in peripheral blood of patients with UC as compared with Crohn's disease and controls. In vivo analysis in a humanised mouse model showed augmented gut homing of UC Treg cells as compared with controls. Moreover, suppression of UC (but not control) Teff and Treg cell homing was noted upon treatment with the α4β7 antibody vedolizumab. In contrast, siRNA blockade of GPR15 had only effects on homing of Teff cells but did not affect Treg homing in UC. Clinical vedolizumab treatment was associated with marked expansion of UC Treg cells in peripheral blood. α4β7 rather than GPR15 is crucial for increased colonic homing of UC Treg cells in vivo, while both receptors control UC Teff cell homing. Vedolizumab treatment impairs homing of UC Treg cells leading to their accumulation in peripheral blood with subsequent suppression of systemic Teff cell expansion. 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/

Differential effects of α4β7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo

PubMed Central

Fischer, Anika; Zundler, Sebastian; Atreya, Raja; Rath, Timo; Voskens, Caroline; Hirschmann, Simon; López-Posadas, Rocío; Watson, Alastair; Becker, Christoph; Schuler, Gerold; Neufert, Clemens; Atreya, Imke; Neurath, Markus F

2016-01-01

Objective Gut homing of lymphocytes via adhesion molecules has recently emerged as new target for therapy in IBDs. We aimed to analyse the in vivo homing of effector (Teff) and regulatory (Treg) T cells to the inflamed gut via α4β7 and G protein receptor GPR15. Design We assessed the expression of homing receptors on T cells in peripheral blood and inflamed mucosa. We studied the migration pattern and homing of Teff and Treg cells to the inflamed gut using intravital confocal microscopy and FACS in a humanised mouse model in dextran sodium sulfate-treated NSG (NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ) mice. Results Expression of GPR15 and α4β7 was significantly increased on Treg rather than Teff cells in peripheral blood of patients with UC as compared with Crohn’s disease and controls. In vivo analysis in a humanised mouse model showed augmented gut homing of UC Treg cells as compared with controls. Moreover, suppression of UC (but not control) Teff and Treg cell homing was noted upon treatment with the α4β7 antibody vedolizumab. In contrast, siRNA blockade of GPR15 had only effects on homing of Teff cells but did not affect Treg homing in UC. Clinical vedolizumab treatment was associated with marked expansion of UC Treg cells in peripheral blood. Conclusions α4β7 rather than GPR15 is crucial for increased colonic homing of UC Treg cells in vivo, while both receptors control UC Teff cell homing. Vedolizumab treatment impairs homing of UC Treg cells leading to their accumulation in peripheral blood with subsequent suppression of systemic Teff cell expansion. PMID:26209553

Light atom quantum oscillations in UC and US

DOE PAGES

Yiu, Yuen; Aczel, Adam A.; Granroth, Garrett E.; ...

2016-01-19

High energy vibrational scattering in the binary systems UC and US is measured using time-of-flight inelastic neutron scattering. A clear set of well-defined peaks equally separated in energy is observed in UC, corresponding to harmonic oscillations of the light C atoms in a cage of heavy U atoms. The scattering is much weaker in US and only a few oscillator peaks are visible. We show how the difference between the materials can be understood by considering the neutron scattering lengths and masses of the lighter atoms. Monte Carlo ray tracing is used to simulate the scattering, with near quantitative agreementmore » with the data in UC, and some differences with US. The possibility of observing anharmonicity and anisotropy in the potentials of the light atoms is investigated in UC. Lastly, the observed data is well accounted for by considering each light atom as a single atom isotropic quantum harmonic oscillator.« less

Relationship and significance between anti-β2-glycoproteinI antibodies and platelet activation state in patients with ulcerative colitis

PubMed Central

Gao, Yan-Hang; Gao, Pu-Jun; Wang, Chun-Guang; Wang, Xiao-Cong; Piao, Yun-Feng

2008-01-01

AIM: To study the relationship between anti-β2-glycoprotein I (aβ2GPI) antibodies and platelet activation state in patients with ulcerative colitis (UC) and its significance. METHODS: Peripheral blood samples were collected from 56 UC patients (34 males and 22 females, aged 43.5 years, range 21-66 years), including 36 at active stage and 20 at remission stage, and 25 sex-and age-matched controls. The level of aβ2GPI was measured by ELISA. The platelet activation markers, platelet activation complex-I (PAC-I) and P-selectin (CD62P) were detected by flow cytometry. RESULTS: The A value for IgG aβ2GPI in the active UC group was 0.61 ± 0.13, significantly higher than that in the remittent UC and control groups (0.50 ± 0.13 and 0.22 ± 0.14, P < 0.01). There was a significant difference between the two groups (P < 0.01). The A value for IgM aβ2GPI in the active and remittent UC groups was 0.43 ± 0.13 and 0.38 ± 0.12, significantly higher than that in the control group (0.20 ± 0.12, P < 0.01). However, there was no significant difference between the two groups (P > 0.05). The PAC-I positive rate for the active and remittent UC groups was 30.6% ± 7.6% and 19.6% ± 7.8% respectively, significantly higher than that for the control group (6.3% ± 1.7%, P < 0.01). There was a significant difference between the two groups (P < 0.01). The CD62P positive rate for the active and remittent UC groups was 45.0% ± 8.8% and 31.9% ± 7.8% respectively, significantly higher than that for the control group (9.2% ± 2.7%, P < 0.01). There was a significant difference between the two groups (P < 0.01). In the active UC group, the more severe the state of illness was, the higher the A value for IgG aβ2GPI was, and the positive rate for PAC-I and CD62P was positively correlated with the state of illness (Faβ2GPI = 3.679, P < 0.05; FPAC-I (%) = 5.346, P < 0.01; and FCD62P (%) = 5. 418, P < 0.01). Meanwhile, in the same state of illness, the A value for IgG aβ2GPI was positively

Disposition and metabolism of 2,3-( UC)dichloropropene in rats after inhalation

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

Bond, J.A.; Medinsky, M.A.; Dutcher, J.S.

1985-01-01

2,3-Dichloropropene (2,3-DCP) is a constituent of some commercially available preplant soil fumigants for the control of plant parasitic nematodes. The purpose of this investigation was to determine the disposition and metabolism of 2,3-( UC)DCP in rats after inhalation. Male Fischer-344 rats were exposed nose-only to a vapor concentration of 250 nmol 2,3-( UC)DCP/liter air (7.5 ppm; 25C, 620 Torr) for 6 hr. Blood samples were taken during exposure, and urine, feces, expired air, and tissues were collected for up to 65 hr after exposure. Urinary excretion was the major route of elimination of UC (55% of estimated absorbed 2,3-DCP). Half-timemore » for elimination of UC in urine was 9.8 +/- 0.05 hr (anti x +/- SE). Half-time for elimination of UC feces (17% of absorbed 2,3-DCP) was 12.9 +/- 0.14 hr (anti x +/- SE). Approximately 1 and 3% of the estimated absorbed 2,3-( UC)DCP were exhaled as either 2,3-( UC)DCP or UCO2, respectively. Concentrations of UC in blood increased during 240 min of exposure, after which no further increases in blood concentration of UC were seen. UC was widely distributed in tissues analyzed after a 6-hr exposure of rats to 2,3-( UC)DCP. Urinary bladder (150 nmol/g), nasal turbinates (125 nmol/g), kidneys (84 nmol/g), small intestine (61 nmol/g), and liver (35 nmol/g) were tissues with the highest concentrations of UC immediately after exposure. Over 90% of the UC in tissues analyzed was 2,3-DCP metabolites. Half-times for elimination of UC from tissues examined ranged from 3 to 11 hr. The data from this study indicate that after inhalation 2,3-DCP is metabolized in tissues and readily excreted. 21 references. 2 figures, 4 tables.« less

Resveratrol promotes hUC-MSCs engraftment and neural repair in a mouse model of Alzheimer's disease.

PubMed

Wang, Xinxin; Ma, Shanshan; Yang, Bo; Huang, Tuanjie; Meng, Nan; Xu, Ling; Xing, Qu; Zhang, Yanting; Zhang, Kun; Li, Qinghua; Zhang, Tao; Wu, Junwei; Yang, Greta Luyuan; Guan, Fangxia; Wang, Jian

2018-02-26

Mesenchymal stem cell transplantation is a promising therapeutic approach for Alzheimer's disease (AD). However, poor engraftment and limited survival rates are major obstacles for its clinical application. Resveratrol, an activator of silent information regulator 2, homolog 1 (SIRT1), regulates cell destiny and is beneficial for neurodegenerative disorders. The present study is designed to explore whether resveratrol regulates the fate of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and whether hUC-MSCs combined with resveratrol would be efficacious in the treatment of neurodegeneration in a mouse model of AD through SIRT1 signaling. Herein, we report that resveratrol facilitates hUC-MSCs engraftment in the hippocampus of AD mice and resveratrol enhances the therapeutic effects of hUC-MSCs in this model as demonstrated by improved learning and memory in the Morris water maze, enhanced neurogenesis and alleviated neural apoptosis in the hippocampus of the AD mice. Moreover, hUC-MSCs and resveratrol jointly regulate expression of hippocampal SIRT1, PCNA, p53, ac-p53, p21, and p16. These data strongly suggests that hUC-MSCs transplantation combined with resveratrol may be an effective therapy for AD. Copyright © 2017. Published by Elsevier B.V.

9th Annual UC Systemwide Bioengineering Symposium

DTIC Science & Technology

2008-08-01

Morikis UCR CHUNSHENG WANG University of California San Francisco Christopher Druzgalski PAHCE Jeffrey Chen UC Riverside BRITE Adriana Aguirre UC...Diagnosis B23 Foad Mashayekhi, Aaron S. Meyer, Stacey A. Shiigi, Vu Nguyen and Daniel T. Ka - 129 meL UCLA B24 Self-Assembly and DNA Binding Properties of...Journal of Immunclogy 165:3839­ 3848. 2Hannan JP, Young KA , Guthrid!le JM, Asokan R, Szakonyi G, Chen XJS, & Holers \\1M (2005) Journal of Molecular

Rotational Rehybridization and the High Temperature Phase of UC2

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

Wen, Xiaodong; Rudin, Sven P.; Batista, Enrique R.

2012-12-03

The screened hybrid approximation (HSE) of density functional theory (DFT) is used to examine the structural, optical, and electronic properties of the high temperature phase, cubic UC(2). This phase contains C(2) units with a computed C-C distance of 1.443 Å which is in the range of a CC double bond; U is formally 4+, C(2) 4-. The closed shell paramagnetic state (NM) was found to lie lowest. Cubic UC(2) is found to be a semiconductor with a narrow gap, 0.4 eV. Interestingly, the C(2) units connecting two uranium sites can rotate freely up to an angle of 30°, indicating amore » hindered rotational solid. Ab-initio molecular dynamic simulations (HSE) show that the rotation of C(2) units in the low temperature phase (tetragonal UC(2)) occurs above 2000 K, in good agreement with experiment. The computed energy barrier for the phase transition from tetragonal UC(2) to cubic UC(2) is around 1.30 eV per UC(2). What is fascinating about this system is that at high temperature, the phase transformation to the cubic phase is associated with a rehybridization of the C atoms from sp to sp(3).« less

Evaluation of a multiplex PCR assay for detection of cytomegalovirus in stool samples from patients with ulcerative colitis

PubMed Central

Nahar, Saifun; Iraha, Atsushi; Hokama, Akira; Uehara, Ayako; Parrott, Gretchen; Ohira, Tetsuya; Kaida, Masatoshi; Kinjo, Tetsu; Kinjo, Takeshi; Hirata, Tetsuo; Kinjo, Nagisa; Fujita, Jiro

2015-01-01

AIM: To evaluate a multiplex PCR assay for the detection of bacterial and viral enteropathogens in stool samples from patients with ulcerative colitis (UC). METHODS: We prospectively analyzed 300 individuals, including immunocompetent patients, immunocompromised patients, and patients with UC. Stool samples were collected from the recto-sigmoid region of the colon by endoscopy. The samples were qualitatively analyzed for bacterial and viral enteropathogens with a multiplex PCR assay using a Seeplex® Kit. Additional clinical and laboratory data were collected from the medical records. RESULTS: A multiplex PCR assay detected 397 pathogens (191 bacteria and 206 viruses) in 215 samples (71.7%). The most frequently detected bacteria were Escherichia coli H7, 85 (28.3%); followed by Aeromonas spp., 43 (14.3%); and Clostridium perfringens, 36 (12.0%) samples. The most prevalent viruses were Epstein-Barr virus (EBV), 90 (30.0%); followed by human herpes virus-6 (HHV-6), 53 (17.7%); and cytomegalovirus (CMV), 37 (12.3%) samples. The prevalence rate of CMV infection was significantly higher in the immunocompromised group than in the immunocompetent group (P < 0.01). CMV infection was more common in patients with UC (26/71; 36.6%) than in the immunocompetent patients excluding UC (6/188; 3.2%) (P < 0.01). CMV infection was more prevalent in UC active patients (25/58; 43.1%) than in UC inactive patients (1/13; 7.7%) (P < 0.05). Among 4 groups which defined by the UC activity and immunosuppressive drugs, the prevalence rate of CMV infection was highest in the UC active patients with immunosuppressive drugs (19/34; 55.8%). Epstein-Barr virus (EBV) infection was more common in the immunocompromised patients excluding UC (18/41; 43.9%) than in the immunocompetent patients excluding UC (47/188; 25.0%) (P < 0.05). The simultaneous presence of CMV and EBV and/or HHV6 in UC active patients (14/58; 24.1%) was greater than in immunocompromised patients excluding UC (5/41; 12.2%) (P < 0

Escherichia coli isolates from inflammatory bowel diseases patients survive in macrophages and activate NLRP3 inflammasome.

PubMed

De la Fuente, Marjorie; Franchi, Luigi; Araya, Daniela; Díaz-Jiménez, David; Olivares, Mauricio; Álvarez-Lobos, Manuel; Golenbock, Douglas; González, María-Julieta; López-Kostner, Francisco; Quera, Rodrigo; Núñez, Gabriel; Vidal, Roberto; Hermoso, Marcela A

2014-05-01

Crohn's disease (CD) is a multifactorial pathology associated with the presence of adherent-invasive Escherichia coli (AIEC) and NLRP3 polymorphic variants. The presence of intracellular E. coli in other intestinal pathologies (OIP) and the role of NLRP3-inflammasome in the immune response activated by these bacteria have not been investigated. In this study, we sought to characterize intracellular strains isolated from patients with CD, ulcerative colitis (UC) and OIP, and analyze NLRP3-inflammasome role in the immune response and bactericidal activity induced in macrophages exposed to invasive bacteria. For this, intracellular E. coli isolation from ileal biopsies, using gentamicin-protection assay, revealed a prevalence and CFU/biopsy of E. coli higher in biopsies from CD, UC and OIP patients than in controls. To characterize bacterial isolates, pulsed-field gel electrophoresis (PFGE) patterns, virulence genes, serogroup and phylogenetic group were analyzed. We found out that bacteria isolated from a given patient were closely related and shared virulence factors; however, strains from different patients were genetically heterogeneous. AIEC characteristics in isolated strains, such as invasive and replicative properties, were assessed in epithelial cells and macrophages, respectively. Some strains from CD and UC demonstrated AIEC properties, but not strains from OIP. Furthermore, the role of NLRP3 in pro-inflammatory cytokines production and bacterial elimination was determined in macrophages. E. coli strains induced IL-1β through NLRP3-dependent mechanism; however, their elimination by macrophages was independent of NLRP3. Invasiveness of intracellular E. coli strains into the intestinal mucosa and IL-1β production may contribute to CD and UC pathogenesis. Copyright © 2014 Elsevier GmbH. All rights reserved.

Decreased levels of serum omentin-1 in patients with inflammatory bowel disease.

PubMed

Yin, Jian; Hou, Peng; Wu, Zhiqiang; Nie, Yanxiao

2015-01-10

Inflammation is involved in the mechanism of inflammatory bowel disease (IBD). Omentin, a newly discovered adipokine, is thought to play an anti-inflammatory role. This study aimed to determine whether serum levels of omentin-1 are associated with the presence and disease activity of IBD. This study consisted of 192 patients with IBD: 100 with Crohn's disease [CD], 92 with ulcerative colitis [UC], and 104 healthy subjects. Serum levels of omentin-1 were measured using enzyme-linked immunosorbent assay (ELISA). Serum omentin-1 levels were significantly decreased in CD and UC patients compared with healthy controls. Multivariable logistic regression analysis revealed that serum omentin-1 levels were inversely associated with the presence of CD and UC. Active CD and UC patients both had significantly decreased levels of serum omentin-1 compared with inactive CD and UC patients. In both CD and UC patients, serum omentin-1 levels were significantly associated with decreased levels of body mass index (BMI) and C-reactive protein (CRP). Decreased serum omentin-1 levels could be considered as an independent predicting marker of the presence and disease activity of IBD.

Approach to cytomegalovirus infections in patients with ulcerative colitis

PubMed Central

Park, Sung Chul; Jeen, Yoon Mi; Jeen, Yoon Tae

2017-01-01

Cytomegalovirus (CMV) reactivation is common in patients with severe ulcerative colitis (UC), and may ref lect exacerbation of mucosal inf lammation and/or administration of immunosuppressants. The question of whether CMV is an active pathogen or ‘an innocent bystander’ in the exacerbation of UC remains controversial. Patients with UC exacerbated by reactivated CMV experience worse prognoses than those without CMV reactivation and antiviral therapy significantly reduces the need for colectomy in patients with severe UC and high-grade CMV infection, indicating that CMV plays a role in UC prognosis. Therefore, the CMV status of patients on immunosuppressants, particularly those with steroid-refractory or -dependent UC, should be tested. When CMV is detected, be performed based on should adequate treatment the extent of the viral load and the presence of certain clinical features including a large ulcer. Anti-tumor necrosis factor agents may be useful for treating CMV colitis complicating UC. PMID:28490715

[Clinical analysis of cutaneous manifestations and related factors in patients with ulcerative colitis].

PubMed

Tian, Y; Li, J X; Wang, H H; Li, R Y; Liu, X G

2016-07-01

To investigate the cutaneous manifestations in patients with ulcerative colitis (UC) and related factors. Patients admitted to Department of Gastroenterology Peking University First Hospital from January 1994 to December 2014 and diagnosed as UC were retrospectively enrolled in this study. Skin disorders were confirmed by the dermatologists. Clinical data were collected and compared between patients with and without cutaneous manifestations. Among the total 373 UC patients, there were 34 cases (9.1%) with cutaneous manifestations, including 11 pyoderma gangrenosum, 8 erythema nodosum, 6 eczema, 3 psoriasis, 2 pemphigus, 1 granulomatous cheilitis, 1 ichthyosis, 1 acne rosacea, and 1 impetigo. The skin manifestations may occur after the diagnosis, simultaneously or even before the diagnosis of UC, which were 24, 7 and 3 patients respectively. The mean age in patients with skin lesions was (47.2±12.1) years, male to female ratio 0.79∶1. More patients with skin manifestations had severe activity of UC compared with non-skin group [50.0%(17/34) vs 25.1%(85/339), P=0.01]. In addition, the proportion of extensive colitis in skin lesion group was significantly higher than that in non-skin group [76.5%(26/34) vs 54.6%(185/339), P=0.04]. The cutaneous manifestations associated with UC are polymorphic, erythema nodosums and pyoderma gangrenosums are the most common skin lesions seen in UC patients. Skin lesions occur concurrently, pre or post the diagnosis of UC. Skin lesions in UC patients suggest more severe disease activity. Clinicians need to pay more attention to this group.

Approaches to improve the stability of the antiviral agent UC781 in aqueous solutions.

PubMed

Damian, Festo; Fabian, Judit; Friend, David R; Kiser, Patrick F

2010-08-30

In this work, we evaluated the chemical stability profiles of UC781 based solutions to identify excipients that stabilize the microbicidal agent UC781. When different antioxidants were added to UC781 in sulfobutylether-beta-cyclodextrin (SBE-beta-CD) solutions and subjected to a 50 degrees C stability study, it was observed that EDTA was a better stabilizing agent than sodium metabisulfite, glutathione or ascorbic acid. Some antioxidants accelerated the degradation of UC781, suggesting metal-catalyzed degradation of UC781. Furthermore, we observed substantial degradation of UC781 when stored in 1% Tween 80 and 1% DMSO solutions alone or in those with 10mM EDTA. On the other hand, improved stability of UC781 in the presence of 100 and 200mM of EDTA was observed in these solutions. The addition of both EDTA and citric acid in the stock solutions resulted in recovery of more than 60% of UC781 after 12 weeks. Generally, 10% SBE-beta-CD in the presence of EDTA and citric acid stabilized UC781 solutions: the amount of UC781 recovered approaching 95% after 12 weeks of storage at 40 degrees C. We also showed that the desulfuration reaction of the UC781 thioamide involves oxygen by running solution stability studies in deoxygenated media. Improved stability of UC781 in the present study indicates that the incorporation of EDTA, citric acid and SBE-beta-CD and the removal of oxygen in formulations of this drug will aid in increasing the stability of UC781 where solutions of the drug are required. Published by Elsevier B.V.

Reduced risk of UC in families affected by appendicitis: a Danish national cohort study.

PubMed

Nyboe Andersen, Nynne; Gørtz, Sanne; Frisch, Morten; Jess, Tine

2017-08-01

The possible aetiological link between appendicitis and UC remains unclear. In order to investigate the hereditary component of the association, we studied the risk of UC in family members of individuals with appendicitis. A cohort of 7.1 million individuals was established by linkage of national registers in Denmark with data on kinship and diagnoses of appendicitis and UC. Poisson regression models were used to calculate first hospital contact rate ratios (RR) for UC with 95% CIs between individuals with or without relatives with a history of appendicitis. During 174 million person-years of follow-up between 1977 and 2011, a total of 190 004 cohort members developed appendicitis and 45 202 developed UC. Individuals having a first-degree relative with appendicitis before age 20 years had significantly reduced risk of UC (RR 0.90; 95% CI 0.86 to 0.95); this association was stronger in individuals with a family predisposition to UC (RR 0.66; 95% CI 0.51 to 0.83). Individuals with a first-degree relative diagnosed with appendicitis before age 20 years are at reduced risk of UC, particularly when there is a family predisposition to UC. Our findings question a previously hypothesised direct protective influence of appendicitis on inflammation of the large bowel. Rather, genetic or environmental factors linked to an increased risk of appendicitis while being protective against UC may explain the repeatedly reported reduced relative risk of UC in individuals with a history of appendicitis. 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/.

Associations between diet and disease activity in ulcerative colitis patients using a novel method of data analysis

PubMed Central

Magee, Elizabeth A; Edmond, Laurie M; Tasker, Shiona M; Kong, San Choon; Curno, Richard; Cummings, John H

2005-01-01

Background The relapsing nature and varying geographical prevalence of ulcerative colitis (UC) implicates environmental factors such as diet in its aetiology. Methods In order to determine which foods might be related to disease activity in UC a new method of dietary analysis was developed and applied. Eighty-one UC patients were recruited at all stages of the disease process. Following completion of a 7 d diet diary, clinical assessment including a sigmoidoscopic examination (scale 0 (normal mucosa) to 6 (very active disease)) was conducted. Food weights for each person were adjusted (divided) by the person's calorific intake for the week. Each food consumed was given a food sigmoidoscopy score (FSS) calculated by summing the products of the (adjusted) weight of food consumed and sigmoidoscopy score for each patient and occurrence of food and dividing by the total (adjusted) weight of the food consumed by all 81 patients. Thus, foods eaten in large quantities by patients with very active disease have high FSSs and vice versa. Foods consumed by <10 people or weighing <1 kg for the whole group were excluded, leaving 75 foods. Results High FSS foods were characterized by high levels of the anti-thiamin additive sulfite (Mann-Whitney, p < 0.001), i.e. bitter, white wine, burgers, soft drinks from concentrates, sausages, lager and red wine. Caffeine also has anti-thiamin properties and decaffeinated coffee was associated with a better clinical state than the caffeine containing version. Beneficial foods (average intake per week) included pork (210 g), breakfast cereals (200 g), lettuce (110 g), apples and pears (390 g), milk (1250 ml), melon (350 g), bananas (350 g), bacon (120 g), beef and beef products (500 g), tomatoes (240 g), soup (700 g), citrus fruits (300 g), fish (290 g), yogurt (410 g), cheese (110 g), potatoes (710 g) and legumes (120 g). Conclusions The dietary analysis method described provides a new tool for establishing relationships between diet and

46 CFR 54.25-3 - Steel plates (modifies UCS-6).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Steel plates (modifies UCS-6). 54.25-3 Section 54.25-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-3 Steel plates (modifies UCS-6). The steels...

46 CFR 54.25-3 - Steel plates (modifies UCS-6).

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Steel plates (modifies UCS-6). 54.25-3 Section 54.25-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-3 Steel plates (modifies UCS-6). The steels...

46 CFR 54.25-3 - Steel plates (modifies UCS-6).

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Steel plates (modifies UCS-6). 54.25-3 Section 54.25-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-3 Steel plates (modifies UCS-6). The steels...

46 CFR 54.25-3 - Steel plates (modifies UCS-6).

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Steel plates (modifies UCS-6). 54.25-3 Section 54.25-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-3 Steel plates (modifies UCS-6). The steels...

46 CFR 54.25-3 - Steel plates (modifies UCS-6).

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Steel plates (modifies UCS-6). 54.25-3 Section 54.25-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-3 Steel plates (modifies UCS-6). The steels...

Investigation of novel biomarkers for predicting the clinical course in patients with ulcerative colitis.

PubMed

Hamanaka, Shinsaku; Nakagawa, Tomoo; Hiwasa, Takaki; Ohta, Yuki; Kasamatsu, Shingo; Ishigami, Hideaki; Taida, Takashi; Okimoto, Kenichiro; Saito, Keiko; Maruoka, Daisuke; Matsumura, Tomoaki; Takizawa, Hirotaka; Kashiwado, Koichi; Kobayashi, Sohei; Matsushita, Kazuyuki; Matsubara, Hisahiro; Katsuno, Tatsuro; Arai, Makoto; Kato, Naoya

2018-06-05

The clinical course of ulcerative colitis (UC) is characterized by repeated episodes of relapse and remission. We hypothesized that biomarkers that help distinguish refractory UC patients who are in remission using strong anti-immunotherapy could contribute in preventing the overuse of corticosteroids for treatment. Here we clarified novel autoantibodies for UC patients in remission as clinical indicators to distinguish between refractory and non-refractory UC. Antigen proteins recognized by serum antibodies of patients with UC in remission were screened using the protein array method. To validate the results, AlphaLISA was used to analyze the serum antibody titers with candidate protein antigens. Serum samples from 101 healthy controls, 121 patients with UC, and 39 patients with Crohn's disease were analyzed. Of 66 candidate protein antigens screened by ProtoArray™, 6 were selected for this study. The serum titers of anti-poly ADP-ribose glycohydrolase (PARG), anti-transcription elongation factor A protein-like 1 (TCEAL1), and anti-proline-rich 13 (PRR13) antibodies were significantly higher in patients with UC than in healthy controls. Anti-PARG and anti-PRR13 antibody titers were significantly higher in patients with refractory UC than in patients with non-refractory UC. There were no significant differences in any antibody titer between the active and remission phases. The serum titers of anti-PARG, anti-TCEAL1, and anti-PRR13 antibodies were elevated in patients with UC. Anti-PARG and anti-PRR13 antibody titers may be novel clinical indicators for detecting refractory UC in patients in remission. This article is protected by copyright. All rights reserved.

Text Messaging to Improve Disease Management in Patients With Painful Diabetic Peripheral Neuropathy.

PubMed

Bauer, Victoria; Goodman, Nancy; Lapin, Brittany; Cooley, Camille; Wang, Ed; Craig, Terri L; Glosner, Scott E; Juhn, Mark S; Cappelleri, Joseph C; Sadosky, Alesia B; Masi, Christopher

2018-06-01

Purpose The purpose of the study was to determine the impact of educational text messages on diabetes self-management activities and outcomes in patients with painful diabetic peripheral neuropathy (pDPN). Methods Patients with pDPN identified from a large integrated health system who agreed to participate were randomized to 6 months of usual care (UC) or UC plus twice-daily diabetes self-management text messages (UC+TxtM). Outcomes included the Pain Numerical Rating Scale, Summary of Diabetes Self-Care Activities (SDSCA), questions on diabetes health beliefs, and glycated hemoglobin (A1C). Changes from baseline were evaluated at 6 months and compared between groups. Results Demographic characteristics were balanced between groups (N = 62; 53% female, mean age = 63 years, 94% type 2 diabetes), as were baseline measures. After 6 months, pain decreased with UC+TxtM from 6.3 to 5.5 and with UC from 6.5 to 6.0, with no difference between groups. UC+TxtM but not UC was associated with significant improvements from baseline on all SDSCA subscales. On diabetes health beliefs, UC+TxtM patients reported significantly increased benefits and reduced barriers and susceptibility relative to UC at 6 months. A1C declined in both groups, but neither change was significant relative to baseline. Conclusions Patients with pDPN who receive twice-daily text messages regarding diabetes management reported reduced pain relative to baseline, although this change was not significant compared with usual care. In addition, text messaging was associated with increased self-management activities and improved diabetes health beliefs and total self-care. These results warrant further investigation.

What do patients with urothelial cancer know about the association of their tumor disease with smoking habits? Results of a German survey study

PubMed Central

Fritsche, Hans-Martin; Gilfrich, Christian; Dombrowski, Mirja; Maurer, Odilo; Spachmann, Philipp; Kumar, Manju Ganesh; Bjurlin, Marc; Burger, Maximilian; Brookman-May, Sabine

2018-01-01

Purpose Smoking represents a primary risk factor for the development of urothelial carcinoma (UC) and a relevant factor impacting UC-specific prognosis. Data on the accordant knowledge of UC-patients in this regard and the significance of physicians in the education of UC-patients is limited. Materials and Methods Eighty-eight UC-patients were enrolled in a 23-items-survey-study aimed to analyse patient knowledge and awareness of their tumor disease with smoking along with physician smoking cessation counselling. Results The median age of the study patients was 69 years; 26.1% (n=23), 46.6% (n=41), and 27.3% (n=24), respectively, were non-smokers, previous, and active smokers. Exactly 50% of active smokers reported a previous communication with a physician about the association of smoking and their tumor disease; however, only 25.0% were aware of smoking as main risk factor for UC development. Merely 33% of the active smokers had been prompted directly by their physicians to quit smoking. About 42% of active smokers had received the information that maintaining smoking could result in a tumor-specific impairment of their prognosis. Closely 29% of active and about 5% of previous smokers (during the time-period of active smoking) had been offered support from physicians for smoking cessation. No association was found between smoking anamnesis (p=0.574) and pack-years (p=0.912), respectively, and tumor stage of UC. Conclusions The results of this study suggest that the medical conversation of physicians with UC-patients about the adverse significance of smoking is limited. Implementation of structured educational programs for smoking cessation may be an opportunity to further enhance comprehensive cancer care. PMID:29520384

Medical Therapy of Active Ulcerative Colitis

PubMed Central

Bürger, Martin; Schmidt, Carsten; Teich, Niels; Stallmach, Andreas

2015-01-01

Summary Background Medical therapy of mild and moderate ulcerative colitis (UC) of any extent is evidence-based and standardized by national and international guidelines. However, patients with steroid-refractory UC still represent a challenge. Methods A literature search using PubMed (search terms: ulcerative colitis, therapy, new, 1-2008-2015) resulted in 821 publications. For the current article, 88 citations were extracted including 36 randomized controlled studies, 18 reviews, and 8 meta-analyses. Results In steroid-refractory UC, early intensive therapy using anti-tumor necrosis factor (TNF) antibodies or the calcineurin inhibitors cyclosporine and tacrolimus is indicated in any case to prevent progression to a toxic megacolon and/or to avoid proctocolectomy. In patients with chronic disease activity, treatment with anti-TNF antibodies has a higher level of evidence than azathioprine therapy and should therefore be preferred. However, there is a subgroup of UC patients who may achieve prolonged steroid-free remission on azathioprine monotherapy. The importance of vedolizumab, a newly registered inhibiting antibody against integrin, has not yet been fully clarified since direct comparison studies are lacking, in particular in relation to anti-TNF antibodies. Conclusion There is a great need for additional innovative therapies, especially in cases of primary non-response or secondary loss of response to anti-TNF antibodies. New small molecules (Janus kinase inhibitors) are promising with an acceptable safety profile and efficacy in UC. Further, strategies that target the intestinal microbiome are currently considered for patients with active or relapsing UC, and may in the future open up new therapeutic options. PMID:26557831

Frequency and prognostic role of mucosal healing in patients with Crohn’s disease and ulcerative colitis after one-year of biological therapy

PubMed Central

Farkas, Klaudia; Lakatos, Péter László; Szűcs, Mónika; Pallagi-Kunstár, Éva; Bálint, Anita; Nagy, Ferenc; Szepes, Zoltán; Vass, Noémi; Kiss, Lajos S; Wittmann, Tibor; Molnár, Tamás

2014-01-01

AIM: To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn’s disease (CD) and ulcerative colitis (UC). METHODS: The data from 41 patients with CD and 22 patients with UC were assessed. Twenty-four CD patients received infliximab, and 17 received adalimumab. The endoscopic severity of CD was quantified with the simplified endoscopic activity score for Crohn’s disease in CD and with the Mayo endoscopic subscore in UC. RESULTS: Mucosal healing was achieved in 23 CD and 7 UC patients. Biological therapy had to be restarted in 78% of patients achieving complete mucosal healing with CD and in 100% of patients with UC. Neither clinical remission nor mucosal healing was associated with the time to restarting the biological therapy in either CD or UC. CONCLUSION: Mucosal healing did not predict sustained clinical remission in patients in whom the biological therapies had been stopped. PMID:24659890

46 CFR 54.25-10 - Low temperature operation-ferritic steels (replaces UCS-65 through UCS-67).

Code of Federal Regulations, 2013 CFR

2013-10-01

... the following additional requirements: Note: For high alloy steels refer to § 54.25-15. For heat... tempered steels. The ultimate and yield strengths shall be as shown in the applicable specification and... 46 Shipping 2 2013-10-01 2013-10-01 false Low temperature operation-ferritic steels (replaces UCS...

46 CFR 54.25-10 - Low temperature operation-ferritic steels (replaces UCS-65 through UCS-67).

Code of Federal Regulations, 2014 CFR

2014-10-01

... the following additional requirements: Note: For high alloy steels refer to § 54.25-15. For heat... tempered steels. The ultimate and yield strengths shall be as shown in the applicable specification and... 46 Shipping 2 2014-10-01 2014-10-01 false Low temperature operation-ferritic steels (replaces UCS...

46 CFR 54.25-10 - Low temperature operation-ferritic steels (replaces UCS-65 through UCS-67).

Code of Federal Regulations, 2012 CFR

2012-10-01

... the following additional requirements: Note: For high alloy steels refer to § 54.25-15. For heat... tempered steels. The ultimate and yield strengths shall be as shown in the applicable specification and... 46 Shipping 2 2012-10-01 2012-10-01 false Low temperature operation-ferritic steels (replaces UCS...

Nutritional status in patients with active inflammatory bowel disease: prevalence of malnutrition and methods for routine nutritional assessment.

PubMed

Mijac, Dragana D; Janković, Goran L J; Jorga, Jagoda; Krstić, Miodrag N

2010-08-01

Malnutrition is a common feature of inflammatory bowel disease (IBD). There are numerous methods for the assessment of nutritional status, but the gold standard has not yet been established. The aims of the study were to estimate the prevalence of undernutrition and to evaluate methods for routine nutritional assessment of active IBD patients. Twenty-three patients with active Crohn disease, 53 patients with active ulcerative colitis and 30 controls were included in the study. The nutritional status was assessed by extensive anthropometric measurements, percentage of weight loss in the past 1-6 months and biochemical markers of nutrition. All investigated nutritional parameters were significantly different in IBD patients compared to control subjects, except MCV, tryglicerides and serum total protein level. Serum albumin level and body mass index (BMI) were the most predictive parameters of malnutrition. According to different assessment methods the prevalence of undernutrition and severe undernutrition in patients with active IBD were 25.0%-69.7% and 1.3%-31.6%, respectively, while in the control subjects no abnormalities have been detected. There was no statistically significant difference of nutritional parameters between UC and CD patients except lower mid-arm muscle circumference in UC group. Malnutrition is common in IBD patients. BMI and serum albumin are simple and convenient methods for the assessment of the nutritional status in IBD patients. Further studies with larger group of patients are necessary to elucidate the prevalence of malnutrition and the most accurate assessment methods in IBD patients.

Undenatured type II collagen (UC-II®) for joint support: a randomized, double-blind, placebo-controlled study in healthy volunteers

PubMed Central

2013-01-01

Background UC-II contains a patented form of undenatured type II collagen derived from chicken sternum. Previous preclinical and clinical studies support the safety and efficacy of UC-II in modulating joint discomfort in osteoarthritis and rheumatoid arthritis. The purpose of this study was to assess the efficacy and tolerability of UC-II in moderating joint function and joint pain due to strenuous exercise in healthy subjects. Methods This randomized, double-blind, placebo-controlled study was conducted in healthy subjects who had no prior history of arthritic disease or joint pain at rest but experienced joint discomfort with physical activity. Fifty-five subjects who reported knee pain after participating in a standardized stepmill performance test were randomized to receive placebo (n = 28) or the UC-II (40 mg daily, n = 27) product for 120 days. Joint function was assessed by changes in degree of knee flexion and knee extension as well as measuring the time to experiencing and recovering from joint pain following strenuous stepmill exertion. Results After 120 days of supplementation, subjects in the UC-II group exhibited a statistically significant improvement in average knee extension compared to placebo (81.0 ± 1.3º vs 74.0 ± 2.2º; p = 0.011) and to baseline (81.0 ± 1.3º vs 73.2 ± 1.9º; p = 0.002). The UC-II cohort also demonstrated a statistically significant change in average knee extension at day 90 (78.8 ± 1.9º vs 73.2 ± 1.9º; p = 0.045) versus baseline. No significant change in knee extension was observed in the placebo group at any time. It was also noted that the UC-II group exercised longer before experiencing any initial joint discomfort at day 120 (2.8 ± 0.5 min, p = 0.019), compared to baseline (1.4 ± 0.2 min). By contrast, no significant changes were seen in the placebo group. No product related adverse events were observed during the study. At study conclusion, five

Undenatured type II collagen (UC-II®) for joint support: a randomized, double-blind, placebo-controlled study in healthy volunteers.

PubMed

Lugo, James P; Saiyed, Zainulabedin M; Lau, Francis C; Molina, Jhanna Pamela L; Pakdaman, Michael N; Shamie, Arya Nick; Udani, Jay K

2013-10-24

UC-II contains a patented form of undenatured type II collagen derived from chicken sternum. Previous preclinical and clinical studies support the safety and efficacy of UC-II in modulating joint discomfort in osteoarthritis and rheumatoid arthritis. The purpose of this study was to assess the efficacy and tolerability of UC-II in moderating joint function and joint pain due to strenuous exercise in healthy subjects. This randomized, double-blind, placebo-controlled study was conducted in healthy subjects who had no prior history of arthritic disease or joint pain at rest but experienced joint discomfort with physical activity. Fifty-five subjects who reported knee pain after participating in a standardized stepmill performance test were randomized to receive placebo (n = 28) or the UC-II (40 mg daily, n = 27) product for 120 days. Joint function was assessed by changes in degree of knee flexion and knee extension as well as measuring the time to experiencing and recovering from joint pain following strenuous stepmill exertion. After 120 days of supplementation, subjects in the UC-II group exhibited a statistically significant improvement in average knee extension compared to placebo (81.0 ± 1.3º vs 74.0 ± 2.2º; p = 0.011) and to baseline (81.0 ± 1.3º vs 73.2 ± 1.9º; p = 0.002). The UC-II cohort also demonstrated a statistically significant change in average knee extension at day 90 (78.8 ± 1.9º vs 73.2 ± 1.9º; p = 0.045) versus baseline. No significant change in knee extension was observed in the placebo group at any time. It was also noted that the UC-II group exercised longer before experiencing any initial joint discomfort at day 120 (2.8 ± 0.5 min, p = 0.019), compared to baseline (1.4 ± 0.2 min). By contrast, no significant changes were seen in the placebo group. No product related adverse events were observed during the study. At study conclusion, five individuals in the UC-II cohort

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

LncRNA uc.48+ is involved in diabetic neuropathic pain mediated by the P2X3 receptor in the dorsal root ganglia.

PubMed

Wang, Shouyu; Xu, Hong; Zou, Lifang; Xie, Jinyang; Wu, Hong; Wu, Bing; Yi, Zhihua; Lv, Qiulan; Zhang, Xi; Ying, Mofeng; Liu, Shuangmei; Li, Guilin; Gao, Yun; Xu, Changshui; Zhang, Chunping; Xue, Yun; Liang, Shangdong

2016-03-01

Some long non-coding RNAs (lncRNAs) participate in physiological processes that maintain cellular and tissue homeostasis, and thus, the dysregulated expression of lncRNAs is involved in the onset and progression of many pathological conditions. Research has indicated that the genetic knockout of some lncRNAs in mice resulted in peri- or postnatal lethality or developmental defects. Diabetes mellitus (DM) is a major cause of peripheral neuropathy. Our studies showed that the expression levels of lncRNA uc.48+ in the diabetic rat dorsal root ganglia (DRG) and the DM patients' serum samples were increased. It suggested that lncRNA uc.48+ was involved in the pathophysiological process of DM. The aim of this study was to investigate the effects of lncRNA uc.48+ small interfering RNA (siRNA) on diabetic neuropathic pain (DNP) mediated by the P2X3 receptor in the DRG. The values of the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured by the von Frey test and Hargreaves' test, respectively. The levels of P2X3 protein and messenger RNA (mRNA) in the DRG were detected by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and western blotting. The experiments showed that the MWT and TWL values in DM rats were lower than those in the control rats. The MWT and TWL values in DM rats treated with lncRNA uc.48+ siRNA were increased compared to those in DM rats, but there was no significant difference between the DM rat group and the DM + scramble siRNA group. The levels of P2X3 protein and mRNA in the DM DRG were higher than those in the control, while the levels of P2X3 protein and mRNA in the DG of DM rats treated with uc.48+ siRNA were significantly decreased compared to those in DM rats. The expression levels of TNF-α in the DRG of DM rats treated with uc.48+ siRNA were significantly decreased compared to those in the DM group. The phosphorylation and activation of ERK1/2 in the DM DRG were decreased by

Creating an Engaging Library Orientation: First Year Experience Courses at UC San Diego

ERIC Educational Resources Information Center

Goldman, Crystal; Turnbow, Dominique; Roth, Amanda; Friedman, Lia; Heskett, Karen

2016-01-01

This article focuses on the development of an engaging library orientation module for UC San Diego First Year Experience (FYE) courses. The library module included a brief in-class presentation about research concepts and library services, an online interactive library scavenger hunt given as an in-class activity, and a homework assignment where…

Expression characteristics of long noncoding RNA uc.322 and its effects on pancreatic islet function.

PubMed

Zhao, Xiaoqin; Rong, Can; Pan, Fenghui; Xiang, Lizhi; Wang, Xinlei; Hu, Yun

2018-06-28

Increasing evidence indicates that long noncoding RNAs (lncRNAs) perform special biological functions by regulating gene expression through multiple pathways and molecular mechanisms. The aim of this study was to explore the expression characteristics of lncRNA uc.322 in pancreatic islet cells and its effects on the secretion function of islet cells. Bioinformatics analysis was used to detect the lncRNA uc.322 sequence, location, and structural features. Expression of lncRNA uc.322 in different tissues was detected by quantitative polymerase chain reaction analyses. Quantitative polymerase chain reaction, Western blot analysis, adenosine triphosphate determination, glucose-stimulated insulin secretion, and enzyme-linked immunosorbent assay were used to evaluate the effects of lncRNA uc.322 on insulin secretion. The results showed that the full-length of lncRNA uc.322 is 224 bp and that it is highly conserved in various species. Bioinformatics analysis revealed that lncRNA uc.322 is located on chr7:122893196-122893419 (GRCH37/hg19) within the SRY-related HMG-box 6 gene exon region. Compared with other tissues, lncRNA uc.322 is highly expressed in pancreatic tissue. Upregulation of lncRNA uc.322 expression increases the insulin transcription factors pancreatic and duodenal homeobox 1 and Forkhead box O1 expression, promotes insulin secretion in the extracellular fluid of Min6 cells, and increases the adenosine triphosphate concentration. On the other hand, knockdown of lncRNA uc.322 has opposite effects on Min6 cells. Overall, this study showed that upregulation of lncRNA uc.322 in islet β-cells can increase the expression of insulin transcription factors and promote insulin secretion, and it may be a new therapeutic target for diabetes. © 2018 Wiley Periodicals, Inc.

Dissociation between implicit and explicit responses in postconditioning UCS revaluation after fear conditioning in humans

PubMed Central

Schultz, Douglas H.; Balderston, Nicholas L.; Geiger, Jennifer A.; Helmstetter, Fred J.

2014-01-01

The nature of the relationship between explicit and implicit learning is a topic of considerable debate. In order to investigate this relationship we conducted two experiments on postconditioning revaluation of the unconditional stimulus (UCS) in human fear conditioning. In Experiment 1, the intensity of the UCS was decreased following acquisition for one group (devaluation) and held constant for another group (control). A subsequent test revealed that even though both groups exhibited similar levels of UCS expectancy, the devaluation group had significantly smaller conditional skin conductance responses. The devaluation effect was not explained by differences in the explicit estimates of UCS probability or explicit knowledge that the UCS intensity had changed. In Experiment 2, the value of the UCS was increased following acquisition for one group (inflation) and held constant for another group (control). Test performance revealed that UCS inflation did not alter expectancy ratings, but the inflation group exhibited larger learned skin conductance responses than the control group. The inflation effect was not explained by differences in the explicit estimates of UCS probability or explicit knowledge that the UCS intensity had changed. The SCR revaluation effect was not dependent on explicit memory processes in either experiment. In both experiments we found differences on an implicit measure of learning in the absence of changes in explicit measures. Together, the differences observed between expectancy measures and skin conductance support the idea that these responses might reflect different types of memory formed during the same training procedure and be supported by separate neural systems. PMID:23731073

Intestinal protozoa infections among patients with ulcerative colitis: prevalence and impact on clinical disease course.

PubMed

Yamamoto-Furusho, Jesús K; Torijano-Carrera, Emma

2010-01-01

Epidemiological and microbiologic studies suggest that enteropathogenic microorganisms play a substantial role in the clinical initiation and relapses of inflammatory bowel disease. To explore the prevalence of intestinal protozoa in patients with ulcerative colitis (UC) and its impact on clinical disease course. A total of 215 patients with definitive diagnosis of UC were studied. Fresh feces samples taken from all UC patients were examined immediately using trichrome-staining methods. A total of 103 female and 112 male UC patients were analyzed. The mean age at diagnosis was 30.5 +/- 10.8 years. The prevalence of overall parasitic infections was 24% and distributed as follows: Blastocystis hominis in 22 patients (10%), Endolimax nana in 19 cases (9%), and Entamoebahistolytica in 11 cases (5%). A significantly increased frequency of protozoa infection was found in those patients with persistent activity and intermittent activity as compared to active than inactive group (p = 1 x 10(-7), OR 13.05, 95% CI 4.28-42.56, and p = 0.003, OR 1.42-14.47, respectively). Interestingly, this association remained significant when we compared the persistent activity group versus intermittent activity group (p = 0.003, OR 2.97, 95% CI 1.35-6.59). Subgroup analysis showed no association between protozoa infection (E. histolytica, B. hominis, and E. nana) and other clinical variables such as gender, extent of disease, extraintestinal complications, medical treatment and grade of disease activity. The prevalence of intestinal protozoa infections in Mexican UC patients was 24% and these microorganisms could be a contributing cause of persistent activity despite medical treatment in our population. 2010 S. Karger AG, Basel.

Histological and immunological features of appendix in patients with ulcerative colitis.

PubMed

Jo, Yukihiko; Matsumoto, Takayuki; Yada, Shinichiro; Nakamura, Shotaro; Yao, Takashi; Hotokezaka, Masayuki; Mibu, Ryuichi; Iida, Mitsuo

2003-01-01

Patients with ulcerative colitis (UC) have a less frequent prior history of appendectomy than the general population. The aim of the present investigation was to elucidate histological and immunological characteristics of the appendix in UC and to assess the effect of appendectomy on the disease. Nine subjects with mildly active UC were treated by surgical appendectomy. In four subjects, the histological findings of the appendix were compatible with ulcerative appendicitis. CD3+CD4+CD25+, CD3+CD4+CD45RO+, and CD3+CD8+CD45RO+ appendiceal mononuclear cells were significantly higher in UC than in acute appendicitis and in normal appendix. There was a trend towards higher mRNA transcripts of IFN-gamma in the appendix of UC than those in other two groups. Clinical activity index decreased significantly four weeks after the appendectomy, although the effect was transient. The appendix is a site of involvement in UC, where mononuclear cells are presumed to be at a state of basal activation.

Corresponding color datasets and a chromatic adaptation model based on the OSA-UCS system.

PubMed

Oleari, Claudio

2014-07-01

Today chromatic adaptation transforms (CATs) are reconsidered, since their mathematical inconsistency has been shown in Color Res. Appl.38, 188 (2013) and by the CIE technical committee TC 8-11: CIECAM02 Mathematics. In 2004-2005 the author proposed an adaptation transform based on the uniform color scale system of the Optical Society of America (OSA-UCS) [J. Opt. Soc. Am. A21, 677 (2004); Color Res. Appl. 30, 31 (2005)] that transforms the cone-activation stimuli into adapted stimuli. The present work considers all the 37 available corresponding color (CC) datasets selected by CIE and (1) shows that the adapted stimuli obtained from CC data are defined up to an unknown transformation, and an unambiguous definition of the adapted stimuli requires additional hypotheses or suitable experimental data (as it is in the OSA-UCS system); (2) produces a CAT, represented by a linear transformation between CCs, associated with any CC dataset, whose high quality measured in ΔE units discards the possibility of nonlinear transformations; (3) analyzes these color-conversion matrices in a heuristic way with a reference adaptation that is approximately that of the OSA-UCS adapted colors for the D65 illuminant and particularly shows accordance with the Hunt effect and the Bezold-Brücke hue shift; (4) proposes the measurements of CC stimuli with a reference adaptation equal to that of the visual situation of the OSA-UCS system for defining adapted colors for any considered illumination adaptation and therefore for defining a general CAT formula.

High intestinal and systemic levels of decoy receptor 3 (DcR3) and its ligand TL1A in active ulcerative colitis.

PubMed

Bamias, Giorgos; Kaltsa, Garyfallia; Siakavellas, Spyros I; Papaxoinis, Kostis; Zampeli, Evanthia; Michopoulos, Spyros; Zouboulis-Vafiadis, Irene; Ladas, Spiros D

2010-11-01

Decoy receptor-3 (DcR3) is a member of the TNF receptor superfamily of proteins, which has been implicated in anti-apoptotic and anti-inflammatory pathways, via binding to TL1A, LIGHT and Fas-L. The role of the TL1A/DcR3 ligand/receptor pair in ulcerative colitis (UC) has not been studied. We investigated the systemic (peripheral blood) and local (large intestine) expression of DcR3 and TL1A in 64 patients with UC and 56 healthy controls. DcR3 serum concentrations were highly elevated in patients with active UC (P<0.0001 vs. healthy controls). This elevation was clearly related to the presence of intestinal inflammation as it was less frequently observed in patients in remission (P=0.003 vs. active UC) whereas effective treatment resulted in disappearance or significant decrease of serum DcR3 (P=0.006 vs. pre-treatment). Furthermore, DcR3 mRNA transcripts were significantly elevated in inflamed areas of the colon (P=0.002 vs. non-affected of the same patient). In addition to DcR3 elevation, we found increased circulating levels of TL1A in patients with either active or inactive UC in comparison to healthy controls (P<0.001 for both). We conclude that elevated serum DcR3 may serve as an indicator of active colonic inflammation in patients with UC. TL1A/DcR3-mediated pathways may participate in the pathogenesis of UC. Copyright © 2010 Elsevier Inc. All rights reserved.

A Systematic Theoretical Study of UC6: Structure, Bonding Nature, and Spectroscopy.

PubMed

Du, Jiguang; Jiang, Gang

2017-11-20

The study of uranium carbides has received renewed attention in recent years due to the potential use of these compounds as fuels in new generations of nuclear reactors. The isomers of the UC 6 cluster were determined by DFT and ab initio methods. The structures obtained using SC-RECP for U were generally consistent with those obtained using an all-electron basis set (ZORA-SARC). The CCSD(T) calculations indicated that two isomers had similar energies and may coexist in laser evaporation experiments. The nature of the U-C bonds in the different isomers was examined via a topological analysis of the electron density, and the results indicated that the U-C bonds are predominantly closed-shell (ionic) interactions with a certain degree of covalent character in all cases, particularly in the linear species. The IR and UV-vis spectra of the isomers were theoretically simulated to provide information that can be used to identify the isomers of UC 6 in future experiments.

UC Davis Fuel Cell, Hydrogen, and Hybrid Vehicle (FCH2V) GATE Center of Excellence

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

Erickson, Paul

This is the final report of the UC Davis Fuel Cell, Hydrogen, and Hybrid Vehicle (FCH2V) GATE Center of Excellence which spanned from 2005-2012. The U.S. Department of Energy (DOE) established the Graduate Automotive Technology Education (GATE) Program, to provide a new generation of engineers and scientists with knowledge and skills to create advanced automotive technologies. The UC Davis Fuel Cell, Hydrogen, and Hybrid Vehicle (FCH2V) GATE Center of Excellence established in 2005 is focused on research, education, industrial collaboration and outreach within automotive technology. UC Davis has had two independent GATE centers with separate well-defined objectives and research programsmore » from 1998. The Fuel Cell Center, administered by ITS-Davis, has focused on fuel cell technology. The Hybrid-Electric Vehicle Design Center (HEV Center), administered by the Department of Mechanical and Aeronautical Engineering, has focused on the development of plug-in hybrid technology using internal combustion engines. The merger of these two centers in 2005 has broadened the scope of research and lead to higher visibility of the activity. UC Davis's existing GATE centers have become the campus's research focal points on fuel cells and hybrid-electric vehicles, and the home for graduate students who are studying advanced automotive technologies. The centers have been highly successful in attracting, training, and placing top-notch students into fuel cell and hybrid programs in both industry and government.« less

Activated platelets are the source of elevated levels of soluble CD40 ligand in the circulation of inflammatory bowel disease patients.

PubMed

Danese, S; Katz, J A; Saibeni, S; Papa, A; Gasbarrini, A; Vecchi, M; Fiocchi, C

2003-10-01

The CD40/CD40L system, a key regulator and amplifier of immune reactivity, is activated in inflammatory bowel disease (IBD) mucosa. To determine whether plasma levels of sCD40L are elevated in Crohn's disease (CD) and ulcerative colitis (UC) patients compared with normal controls, to investigate the cellular source of sCD40L, and to explore CD40L induction mechanisms. CD, UC, and normal control subjects were studied. The concentration of sCD40L in plasma and supernatants of freshly isolated platelets and autologous peripheral blood T cells (PBT) was measured by ELISA. Surface CD40L expression level was measured by flow cytometry in resting and thrombin activated platelets, and unstimulated and CD3/CD28 stimulated PBT before and after coculture with human intestinal microvascular endothelial cells (HIMEC). Compared with normal controls, plasma sCD40L levels were significantly higher in both CD and UC patients and proportional to the extent of mucosal inflammation. Platelets from IBD patients displayed a significantly higher surface CD40L expression than those from control subjects, and released greater amounts of sCD40L than autologous PBT. Contact with IL-1beta activated HIMEC induced significant upregulation of CD40L surface expression and release by platelets. Elevated levels of sCD40L in the circulation of IBD patients reflect enhanced surface expression and release of CD40L by platelets. This phenomenon translates to an increased platelet activation state apparently induced by passage through an inflamed mucosal microvascular bed, a conclusion supported by the positive correlation of plasma sCD40L levels with the extent of anatomical involvement by IBD. These results suggest that platelet-endothelial interactions critically contribute to activation of the CD40 pathway in IBD.

Prevalence and factors associated with the presence of abnormal function liver tests in patients with ulcerative colitis.

PubMed

Yamamoto-Furusho, Jesús K; Sánchez-Osorio, Magdalena; Uribe, Misael

2010-01-01

To investigate the prevalence of abnormal function liver tests and risk factors associated with their development in Mexican patients with UC. A total of 200 patients with confirmed diagnosis of UC were evaluated prospectively during a one year period from January 1, 2007 to December 31, 2008. A total of 94 females and 106 males patients with UC were analyzed. The age at diagnosis was 31.4 ± 13.2 years and the mean of disease duration was 6.7 ± 5.2 years. We found a high prevalence of abnormal function livers tests in 40% of UC patients. The pattern of abnormal function liver test was hepatitis in 70%, cholestatic (20%) and mixed (10%). The most common cause of abnormal function liver test was transient elevation in 50 patients (63%) followed by fatty liver disease (11.2%), primary sclerosing cholangitis (6.3%), drug-toxicity (6%) and others (13.5%) including chronic hepatitis C, total parenteral nutrition, granulomatous and ischemic hepatitis. In the multivariate logistic regression model, active disease, colectomy and abdominal sepsis were factors that persisted associated with the development of abnormal liver tests in UC patients. A high prevalence of abnormal function liver tests (40%) was found in Mexican UC patients is likely to be related to active disease, colectomy and the presence of sepsis.

Difference in Ulex europaeus agglutinin I-binding activity of decay-accelerating factor detected in the stools of patients with colorectal cancer and ulcerative colitis.

PubMed

Okazaki, Hiroaki; Mizuno, Motowo; Nasu, Junichirou; Makidono, Chiho; Hiraoka, Sakiko; Yamamoto, Kazuhide; Okada, Hiroyuki; Fujita, Teizo; Tsuji, Takao; Shiratori, Yasushi

2004-03-01

Expression of decay-accelerating factor (DAF, CD55), a complement-regulatory glycoprotein, is enhanced in colorectal-cancer (CC) cells and colonic epithelium in ulcerative colitis (UC), and stools from these patients contain increased amounts of DAF. Carbohydrate chains of glycoproteins are often altered during malignant transformation or inflammation. In this study, we investigated whether DAF molecules in patients with CC and those with UC differ with respect to oligosaccharide side chains. We analyzed DAF in stools and homogenates of colonic-tissue specimens obtained from patients with CC or UC using solid-phase enzyme-linked assay and Western blotting for reactivity with the lectins Ulex europaeus agglutinin I (UEA-I), wheat-germ agglutinin, peanut agglutinin, and concanavalin A. UEA-I bound to DAF in stools from patients with UC but not in that from the stools of CC patients, as demonstrated on the solid-phase enzyme-linked assay (P <.05, Mann-Whitney U test) and Western blotting. Binding of UEA-I was specifically inhibited by the addition of fucose. The difference in UEA-I reactivity with DAF was observed also in colonic-tissue homogenates from patients with UC and those with CC. DAF expressed in the mucosa and excreted into the stools of UC patients is different from that expressed in CC with regard to UEA-I reactivity. Future studies should be directed toward determining whether a qualitatively unique isoform of DAF is present, of which sugar chains are specific to CC in UC patients.

Genetic characterization of UCS region of Pneumocystis jirovecii and construction of allelic profiles of Indian isolates based on sequence typing at three regions.

PubMed

Gupta, Rashmi; Mirdha, Bijay Ranjan; Guleria, Randeep; Kumar, Lalit; Luthra, Kalpana; Agarwal, Sanjay Kumar; Sreenivas, Vishnubhatla

2013-01-01

Pneumocystis jirovecii is an opportunistic pathogen that causes severe pneumonia in immunocompromised patients. To study the genetic diversity of P. jirovecii in India the upstream conserved sequence (UCS) region of Pneumocystis genome was amplified, sequenced and genotyped from a set of respiratory specimens obtained from 50 patients with a positive result for nested mitochondrial large subunit ribosomal RNA (mtLSU rRNA) PCR during the years 2005-2008. Of these 50 cases, 45 showed a positive PCR for UCS region. Variations in the tandem repeats in UCS region were characterized by sequencing all the positive cases. Of the 45 cases, one case showed five repeats, 11 cases showed four repeats, 29 cases showed three repeats and four cases showed two repeats. By running amplified DNA from all these cases on a high-resolution gel, mixed infection was observed in 12 cases (26.7%, 12/45). Forty three of 45 cases included in this study had previously been typed at mtLSU rRNA and internal transcribed spacer (ITS) region by our group. In the present study, the genotypes at those two regions were combined with UCS repeat patterns to construct allelic profiles of 43 cases. A total of 36 allelic profiles were observed in 43 isolates indicating high genetic variability. A statistically significant association was observed between mtLSU rRNA genotype 1, ITS type Ea and UCS repeat pattern 4. Copyright © 2012 Elsevier B.V. All rights reserved.

The relationship among multiple patient-reported outcomes measures for patients with ulcerative colitis receiving treatment with MMX ® formulated delayed-release mesalamine.

PubMed

Yarlas, Aaron; Yen, Linnette; Hodgkins, Paul

2015-03-01

Ulcerative colitis (UC) is associated with impaired health-related quality of life (HRQL) and work-related outcomes (WRO). This analysis examined correspondences among measures of HRQL and WRO in patients with UC, as well as the magnitude of each measure's responsiveness to disease activity and treatment. An open-label, prospective trial of delayed-release mesalamine tablets formulated with MMX(®) technology included 8 weeks of treatment for patients with active mild-to-moderate UC (n = 137) and 12 months of maintenance treatment for patients with quiescent UC (n = 206). Spearman correlations (ρ) measured inter-domain associations across measures of generic HRQL [12-item Short-Form Health Survey (SF-12v2)], disease-specific HRQL [Short Inflammatory Bowel Disease Questionnaire (SIBDQ)], and disease-specific WRO [Work Productivity and Activity Impairment for Specific Health Problems (WPAI:SHP)]. Responsiveness to disease activity and treatment was assessed for each instrument. Changes in scores from baseline to week 8 were moderately correlated across all instrument domains: 65 of 80 (81 %) between-instrument inter-domain correlations were of moderate magnitude (0.30 < ρ < 0.70), with an average magnitude of 0.42 [95 % confidence interval (CI) 0.38-0.46]. Associations between symptom measures were stronger for SIBDQ (|average ρ| = 0.41; 95 % CI 0.34-0.48) and WPAI:SHP (0.40; 0.30-0.47) than SF-12v2 (0.30; 0.27-0.34). SIBDQ was most sensitive to treatment [effect size (d z ) for change from baseline to week 8 = 0.62; 95 % CI 0.35-0.89], followed by WPAI:SHP (d z = 0.43; 0.32-0.54) and SF-12v2 (d z = 0.33; 0.27-0.39). While the SIBDQ showed the greatest overall responsiveness to disease activity and treatment, all three patient-reported outcomes instruments provided complementary interpretive information regarding the impact of UC treatment.

Quantification of process variables for carbothermic synthesis of UC1-xNx fuel microspheres

NASA Astrophysics Data System (ADS)

Lindemer, T. B.; Silva, C. M.; Henry, J. J.; McMurray, J. W.; Voit, S. L.; Collins, J. L.; Hunt, R. D.

2017-01-01

This report details the continued investigation of process variables involved in converting sol-gel-derived, urania-carbon microspheres to ∼820-μm-dia. UC1-xNx fuel kernels in flow-through, vertical Mo and W crucibles at temperatures up to 2123 K. Experiments included calcining of air-dried UO3-H2O-C microspheres in Ar and H2-containing gases, conversion of the resulting UO2-C kernels to dense UO2:2UC in the same gases and vacuum, and its conversion in N2 to UC1-xNx (x = ∼0.85). The thermodynamics of the relevant reactions were applied extensively to interpret and control the process variables. Producing the precursor UO2:2UC kernel of ∼96% theoretical density was required, but its subsequent conversion to UC1-xNx at 2123 K was not accompanied by sintering and resulted in ∼83-86% of theoretical density. Increasing the UC1-xNx kernel nitride component to ∼0.98 in flowing N2-H2 mixtures to evolve HCN was shown to be quantitatively consistent with present and past experiments and the only useful application of H2 in the entire process.

Lack of in vitro-in vivo correlation for a UC781-releasing vaginal ring in macaques.

PubMed

McConville, Christopher; Smith, James M; McCoy, Clare F; Srinivasan, Priya; Mitchell, James; Holder, Angela; Otten, Ron A; Butera, Salvatore; Doncel, Gustavo F; Friend, David R; Malcolm, R Karl

2015-02-01

This study describes the preclinical development of a matrix-type silicone elastomer vaginal ring device designed to provide controlled release of UC781, a non-nucleoside reverse transcriptase inhibitor. Testing of both human- and macaque-sized rings in a sink condition in vitro release model demonstrated continuous UC781 release in quantities considered sufficient to maintain vaginal fluid concentrations at levels 82-860-fold higher than the in vitro IC50 (2.0 to 10.4 nM) and therefore potentially protect against mucosal transmission of HIV. The 100-mg UC781 rings were well tolerated in pig-tailed macaques, did not induce local inflammation as determined by cytokine analysis and maintained median concentrations in vaginal fluids of UC781 in the range of 0.27 to 5.18 mM during the course of the 28-day study. Analysis of residual UC781 content in rings after completion of both the in vitro release and macaque pharmacokinetic studies revealed that 57 and 5 mg of UC781 was released, respectively. The pharmacokinetic analysis of a 100-mg UC781 vaginal ring in pig-tailed macaques showed poor in vivo-in vitro correlation, attributed to the very poor solubility of UC781 in vaginal fluid and resulting in a dissolution-controlled drug release mechanism rather than the expected diffusion-controlled mechanism.

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.

Fecal level of calprotectin identifies histologic inflammation in patients with ulcerative colitis in clinical and endoscopic remission.

PubMed

Guardiola, Jordi; Lobatón, Triana; Rodríguez-Alonso, Lorena; Ruiz-Cerulla, Alexandra; Arajol, Claudia; Loayza, Carolina; Sanjuan, Xavier; Sánchez, Elena; Rodríguez-Moranta, Francisco

2014-11-01

Histologic recovery of patients with ulcerative colitis (UC) often is incomplete, even among those in clinical and endoscopic remission. Persistent active microscopic inflammation is associated with an increased risk of relapse and colorectal neoplasia. A high level of fecal calprotectin (FC) is a reliable marker of endoscopic lesions in patients with UC. We evaluated the accuracy of FC in identifying patients with UC in clinical and endoscopic remission who still have histologic features of inflammation. We performed a prospective observational study of 59 patients with UC in clinical and endoscopic remission undergoing colonoscopy. Several biopsy specimens were collected from each colonic segment. Endoscopic remission was defined as a Mayo endoscopic subscore with a grade of 0 or 1. Active histologic inflammation was defined by the presence of neutrophils infiltrating crypt epithelial cells. FC was determined by enzyme-linked immunosorbent assay analysis. Eighteen patients (30.5%) showed evidence of active histologic inflammation. Patients with active histologic inflammation had a significantly higher median level of FC (278 μg/g; interquartile range, 136-696 μg/g) than those without active histologic inflammation (68 μg/g; interquartile range, 30-172 μg/g) (P = .002). In multivariate analysis, the FC and Mayo endoscopic subscore (0 or 1) were each independent predictors of histologic inflammation. The level of FC identified active histologic inflammation in patients in clinical and endoscopic remission, with an area under the receiver operator characteristic curve value of 0.754. Histologic inflammation is common among patients with UC in clinical and endoscopic remission. Patients with histologic features of inflammation can be identified reliably based on their fecal level of calprotectin. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

UC Merced Center for Computational Biology Final Report

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

Colvin, Michael; Watanabe, Masakatsu

Final report for the UC Merced Center for Computational Biology. The Center for Computational Biology (CCB) was established to support multidisciplinary scientific research and academic programs in computational biology at the new University of California campus in Merced. In 2003, the growing gap between biology research and education was documented in a report from the National Academy of Sciences, Bio2010 Transforming Undergraduate Education for Future Research Biologists. We believed that a new type of biological sciences undergraduate and graduate programs that emphasized biological concepts and considered biology as an information science would have a dramatic impact in enabling the transformationmore » of biology. UC Merced as newest UC campus and the first new U.S. research university of the 21st century was ideally suited to adopt an alternate strategy - to create a new Biological Sciences majors and graduate group that incorporated the strong computational and mathematical vision articulated in the Bio2010 report. CCB aimed to leverage this strong commitment at UC Merced to develop a new educational program based on the principle of biology as a quantitative, model-driven science. Also we expected that the center would be enable the dissemination of computational biology course materials to other university and feeder institutions, and foster research projects that exemplify a mathematical and computations-based approach to the life sciences. As this report describes, the CCB has been successful in achieving these goals, and multidisciplinary computational biology is now an integral part of UC Merced undergraduate, graduate and research programs in the life sciences. The CCB began in fall 2004 with the aid of an award from U.S. Department of Energy (DOE), under its Genomes to Life program of support for the development of research and educational infrastructure in the modern biological sciences. This report to DOE describes the research and academic

Serology of Patients with Ulcerative Colitis After Pouch Surgery Is More Comparable with that of Patients with Crohn's Disease.

PubMed

Goren, Idan; Yahav, Lior; Tulchinsky, Hagit; Dotan, Iris

2015-10-01

The serologic status of patients with ulcerative colitis (UC) who develop postoperative pouchitis was compared with that of patients with Crohn's disease (CD) and unoperated patients with UC. Pouch patients were stratified into normal pouch, acute/recurrent acute pouchitis, and chronic pouchitis/Crohn's-like disease of the pouch groups. Antibodies against glycans associated with CD (anti-Saccharomyces cerevisiae, anti-laminaribioside, anti-chitobioside, and anti-mannobioside carbohydrate antibodies [ASCA, ALCA, ACCA, and AMCA, respectively]) were detected and correlated with type of inflammatory bowel disease and pouch behavior. A total of 501 patients with inflammatory bowel diseases were recruited: 250 (50%) CD, 124 (24.7%) unoperated UC, and 127 (25.3%) UC-pouch. At least 1 positive antibody was detected in 77.6% CD, 52.0% UC-pouch and 33.1% unoperated UC (P < 0.0001 for all). ACCA and AMCA prevalence in CD, UC-pouch and unoperated patients with UC were 33.2%, 24.4%, and 16.9% (P = 0.003 for all) and 35.2%, 26.8%, and 7.3%, respectively (P < 0.0001 for all). ALCA and ASCA were more prevalent in patients with CD than unoperated UC and UC-pouch patients. A longer interval since pouch surgery was associated with inflammatory pouch behavior: 12.45, 11.39, and 8.5 years for acute/recurrent acute pouchitis, chronic pouchitis/Crohn's-like disease of the pouch, and normal pouch, respectively, P = 0.01 for all. The prevalence of the CD-associated anti-glycan antibodies ACCA and AMCA is significantly increased in UC-pouch patients, suggesting that pouch surgery may trigger differential immune responses to glycans. The finding that the serology of UC-pouch patients shares similarities with that of patients with CD supports the notion that those 2 inflammatory bowel diseases share a common pathogenic pathway.

Efficacy of vedolizumab for induction of clinical response and remission in patients with moderate to severe inflammatory bowel disease who failed at least two TNF antagonists.

PubMed

De Vos, Martine; Dhooghe, Barbara; Vermeire, Severine; Louis, Edouard; Mana, Fazia; Elewaut, Ann; Bossuyt, Peter; Baert, Filip; Reenaers, Catherine; Van Gossum, Marc; Macken, Elisabeth; Ferrante, Marc; Hindryckx, Pieter; Dewit, Olivier; Holvoet, Tom; Franchimont, Denis

2018-04-01

Vedolizumab is a recently available monoclonal antibody targeting α4β7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). The objective of this article is to evaluate the efficacy of vedolizumab induction therapy in anti-TNF-refractory/intolerant UC and CD patients in real life. A cohort of 149 moderately to severely active UC and CD patients who failed or showed intolerance to at least two TNF antagonists participated in a medical need program and received vedolizumab in 37 Belgian centers (April-September 2015). Rates of clinical response and remission were retrospectively evaluated at Week 10 for UC and Week 14 for CD using the physician's global assessment (PGA), Mayo score and Harvey Bradshaw index (HBI) or Crohn's disease activity score (CDAI) scores. Eighty-four patients (29 UC, 55 CD) had sufficient data for analysis. For UC patients, clinical response was observed in 76% based on PGA and 59% based on the Mayo score. The corresponding percentages for CD patients were 80% for PGA and 65% for HBI/CDAI. Clinical remission rates were 10% and 40% for UC and CD, respectively. Steroid-free remission was observed in respectively 10% and 35%. Globally, corticosteroids were stopped in 14 out of 48 patients (29%). No new safety signals were reported. Up to 70% TNF-refractory/intolerant UC and CD patients achieved a clinical response after 10 to 14 weeks of vedolizumab treatment in this real-life cohort.

A novel UCS memory retrieval-extinction procedure to inhibit relapse to drug seeking.

PubMed

Luo, Yi-xiao; Xue, Yan-xue; Liu, Jian-feng; Shi, Hai-shui; Jian, Min; Han, Ying; Zhu, Wei-li; Bao, Yan-ping; Wu, Ping; Ding, Zeng-bo; Shen, Hao-wei; Shi, Jie; Shaham, Yavin; Lu, Lin

2015-07-14

We recently reported that a conditioned stimulus (CS) memory retrieval-extinction procedure decreases reinstatement of cocaine and heroin seeking in rats and heroin craving in humans. Here we show that non-contingent cocaine or methylphenidate injections (UCS retrieval) 1 h before the extinction sessions decreases cocaine-priming-induced reinstatement, spontaneous recovery, and renewal of cocaine seeking in rats. Unlike the CS-based memory retrieval-extinction procedure, the UCS memory retrieval manipulation decreases renewal and reinstatement of cocaine seeking in the presence of cocaine cues that were not present during extinction training and also decreases cocaine seeking when the procedure commences after 28 days of abstinence. The inhibitory effect of the UCS retrieval manipulation on cocaine-priming-induced reinstatement is mediated by regulation of AMPA-receptor endocytosis in the basolateral amygdala. The UCS memory retrieval-extinction procedure has superior relapse prevention characteristics than the CS memory retrieval-extinction procedure and could be a promising method for decreasing relapse in human addicts.

A novel UCS memory retrieval-extinction procedure to inhibit relapse to drug seeking

PubMed Central

Luo, Yi-xiao; Xue, Yan-xue; Liu, Jian-feng; Shi, Hai-shui; Jian, Min; Han, Ying; Zhu, Wei-li; Bao, Yan-ping; Wu, Ping; Ding, Zeng-bo; Shen, Hao-wei; Shi, Jie; Shaham, Yavin; Lu, Lin

2015-01-01

We recently reported that a conditioned stimulus (CS) memory retrieval-extinction procedure decreases reinstatement of cocaine and heroin seeking in rats and heroin craving in humans. Here we show that non-contingent cocaine or methylphenidate injections (UCS retrieval) 1 h before the extinction sessions decreases cocaine-priming-induced reinstatement, spontaneous recovery, and renewal of cocaine seeking in rats. Unlike the CS-based memory retrieval-extinction procedure, the UCS memory retrieval manipulation decreases renewal and reinstatement of cocaine seeking in the presence of cocaine cues that were not present during extinction training and also decreases cocaine seeking when the procedure commences after 28 days of abstinence. The inhibitory effect of the UCS retrieval manipulation on cocaine-priming-induced reinstatement is mediated by regulation of AMPA-receptor endocytosis in the basolateral amygdala. The UCS memory retrieval-extinction procedure has superior relapse prevention characteristics than the CS memory retrieval-extinction procedure and could be a promising method for decreasing relapse in human addicts. PMID:26169171

Impact of MMX® mesalamine on improvement and maintenance of health-related quality of life in patients with ulcerative colitis.

PubMed

Hodgkins, Paul; Yen, Linnette; Yarlas, Aaron; Karlstadt, Robyn; Solomon, Dory; Kane, Sunanda

2013-02-01

Ulcerative colitis (UC) substantially reduces patients' health-related quality of life (HRQoL). The current study examined the burden of disease and the impact of daily multimatrix (MMX®) mesalamine treatment on HRQoL for patients with active or quiescent mild-to-moderate UC. Data were from a two-phase, multicenter, open-label study with mild-to-moderate UC patients. In the acute phase, 132 patients with active disease received MMX mesalamine 2.4-4.8 g/day QD for 8 weeks. In the maintenance phase, 207 patients with quiescent disease received MMX mesalamine 2.4 g/day QD for 12 months. The Short Form-12 (version 2) (SF-12v2) measured HRQoL during each phase. Disease burden was examined by comparing acute-phase baseline scores with a U.S. general population sample. Repeated-measures analyses assessed change in SF-12v2 scores for each phase. Correspondence between HRQoL and disease activity was examined through correlations between SF-12v2 scores with patient-reported symptom measures. Baseline SF-12v2 scores for patients with UC were generally much lower than for the general population sample, indicating a broad disease burden. In the acute phase, significant improvement was observed for most SF-12v2 scores at week 8; a comparison with the matched norms showed a complete elimination of burden. No changes in SF-12v2 scores were observed during the maintenance phase. Changes in symptom measures and SF-12v2 scores were moderately correlated. The sizeable burden of active mild-to-moderate UC on HRQoL was eliminated following 8 weeks' treatment with MMX mesalamine 2.4-4.8 g/day. HRQoL remained stable over 12 months of maintenance treatment in patients with quiescent UC.

Overexpressed Calponin3 by Subsonic Vibration Induces Neural Differentiation of hUC-MSCs by Regulating the Ionotropic Glutamate Receptor.

PubMed

Kim, Hyun-Jung; Kim, Jin-Hee; Song, Yeo-Ju; Seo, Young-Kwon; Park, Jung-Keug; Kim, Chan-Wha

2015-09-01

In this study, we used proteomics to investigate the effects of sonic vibration (SV) on mesenchymal stem cells derived from human umbilical cords (hUC-MSCs) during neural differentiation to understand how SV enhances neural differentiation of hUC-MSCs. We investigated the levels of gene and protein related to neural differentiation after 3 or 5 days in a group treated with 40-Hz SV. In addition, protein expression patterns were compared between the control and the 40-Hz SV-treated hUC-MSC groups via a proteomic approach. Among these proteins, calponin3 (CNN3) was confirmed to have 299 % higher expression in the 40-Hz SV stimulated hUC-MSCs group than that in the control by Western blotting. Notably, overexpression of CNN3-GFP in Chinese hamster ovary (CHO)-K1 cells had positive effects on the stability and reorganization of F-actin compared with that in GFP-transfected cells. Moreover, CNN3 changed the morphology of the cells by making a neurite-like form. After being subjected to SV, messenger RNA (mRNA) levels of glutamate receptors such as PSD95, GluR1, and NR1 as well as intracellular calcium levels were upregulated. These results suggest that the activity of glutamate receptors increased because of CNN3 characteristics. Taken together, these results demonstrate that overexpressed CNN3 during SV increases expression of glutamate receptors and promotes functional neural differentiation of hUC-MSCs.

46 CFR 54.25-7 - Requirement for postweld heat treatment (modifies UCS-56).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Requirement for postweld heat treatment (modifies UCS-56... for postweld heat treatment (modifies UCS-56). (a) Postweld heat treatment is required for all carbon... the storage or transportation of liquefied compressed gases shall be postweld heat treated regardless...

Thermodynamic and experimental study of UC powders ignition

NASA Astrophysics Data System (ADS)

Le Guyadec, F.; Rado, C.; Joffre, S.; Coullomb, S.; Chatillon, C.; Blanquet, E.

2009-09-01

Mixed plutonium and uranium carbide (UPuC) is considered as a possible fuel material for future nuclear reactors. However, UPuC is pyrophoric and fine powders of UPuC are subject to temperature increase due to oxidation with air and possible ignition during conditioning and handling. In a first approach and to allow easier experimental conditions, this study was undertaken on uranium monocarbide (UC) with the aim to determine safe handling conditions for the production and reprocessing of uranium carbide fuels. The reactivity of uranium monocarbide in oxidizing atmosphere was studied in order to analyze the ignition process. Experimental thermogravimetric analysis (TGA) and differential thermal analysis (DTA) revealed that UC powder obtained by arc melting and milling is highly reactive in air at about 200 °C. The phases formed at the various observed stages of the oxidation process were analyzed by X-ray diffraction. At the same time, ignition was analyzed thermodynamically along isothermal sections of the U-C-O ternary diagram and the pressure of the gas produced by the UC + O 2 reaction was calculated. Two possible oxidation schemes were identified on the U-C-O phase diagram and assumptions are proposed concerning the overall oxidation and ignition paths. It is particularly important to understand the mechanisms involved since temperatures as high as 2500 °C could be reached, leading to CO(g) production and possibly to a blast effect.

Long-Term Benefit of Mesalamine Granules for Patients Who Achieved Corticosteroid-Induced Ulcerative Colitis Remission.

PubMed

Lichtenstein, Gary R; Gordon, Glenn L; Zakko, Salam; Murthy, Uma; Sedghi, Shahriar; Pruitt, Ron; Barrett, Andrew C; Bortey, Enoch; Paterson, Craig; Forbes, William P

2016-01-01

Patients with ulcerative colitis (UC) who achieve remission with corticosteroids often relapse after tapering or discontinuation; alternative treatments limiting steroid exposure and UC relapse would be beneficial. It remains uncertain whether patients with corticosteroid-induced remission experience benefit with mesalamine granules (MG), a locally acting aminosalicylate extended-release capsule formulation for maintenance of UC remission in adults. Efficacy and safety of MG 1.5 g once daily was evaluated in patients with UC in corticosteroid-induced remission. Data from patients with previous corticosteroid use to achieve baseline UC remission were analyzed from two 6-month randomized, double-blind, placebo-controlled trials and a 24-month open-label extension (OLE). Six-month relapse-free rates were assessed using the revised Sutherland Disease Activity Index. UC-related adverse events (AEs) were recorded during the 30 months. Included were 158 steroid-treated patients in UC remission (MG, n = 105; placebo, n = 53) and 74/105 MG-treated patients who continued MG in the OLE. A significantly larger percentage of patients remained relapse-free at 6 months with MG (77.1 %) versus placebo (54.7 %; P = 0.006), with a 55 % reduction in relapse risk (hazard ratio [HR] 0.45; 95 % CI 0.25-0.79). There was a similar (49.2 %) reduction in risk of UC-related AEs at 6 months (HR 0.51; 95 % CI 0.31-0.84; P = 0.009) that was sustained during the OLE. MG 1.5 g once daily administered for maintenance of corticosteroid-induced remission was associated with low risk of relapse and UC-related AEs. CLINICALTRIALS.GOV: NCT00744016, NCT00767728, and NCT00326209.

Treatment efficacy and safety of low-dose azathioprine in chronic active ulcerative colitis patients: A meta-analysis and systemic review.

PubMed

Luan, Zi Jian; Li, Yue; Zhao, Xin Yu; Wang, Li; Sun, Ying Hao; Wang, Shi Yao; Qian, Jia Ming

2016-10-01

To evaluate the efficacy and safety of low-dose azathioprine (AZA) in treating patients with chronic active ulcerative colitis (UC). A literature search of Medline, Embase, the Cochrane Library, Web of Science, Wanfang Database, CNKI, SinoMed, VIP Chinese Science and the Technology Journals Database was conducted to identify eligible studies that evaluated the efficacy and safety of low-dose azathioprine (AZA) in treating patients with chronic active UC published up to 15 July 2015. Data were extracted from the studies, including clinical efficacy (response rate, adverse drug reaction [ADR] rate, steroid withdrawal rate and relapse rate) and endoscopic improvement (endoscopic remission rate and mucosal healing rate). Six studies with 211 patients were eligible for the analysis. The overall response rates after 6 and 12 months of treatment were 78.0% (95% confidence interval [CI] 71.0-85.0%) and 88.0% (95% CI 80.0-96.0%), respectively. The overall ADR rate was 25.0% (95% CI 18.0-31.0%). Endoscopic response rate was around 85.0%, while the endoscopic remission rates and mucosal healing rates after 6 and 12 months of treatment were above 60.0% and 70.0%, respectively. The steroid withdrawal rate and relapse rate were in moderate to high heterogeneity. Egger's test indicated that there was no publication bias for studies regarding the 6-month response rate and ADR rate. Low-dose AZA is effective and safe in the treatment of chronic active UC patients. However, randomized controlled trials with large sample sizes are needed to draw definitive conclusions. © 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Experimental study of UC polycrystals in the prospect of improving the as-fabricated sample purity

NASA Astrophysics Data System (ADS)

Raveu, Gaëlle; Martin, Guillaume; Fiquet, Olivier; Garcia, Philippe; Carlot, Gaëlle; Palancher, Hervé; Bonnin, Anne; Khodja, Hicham; Raepsaet, Caroline; Sauvage, Thierry; Barthe, Marie-France

2014-12-01

Uranium and plutonium carbides are candidate fuels for Generation IV nuclear reactors. This study is focused on the characterization of uranium monocarbide samples. The successive fabrication steps were carried out under atmospheres containing low oxygen and moisture concentrations (typically less than 100 ppm) but sample transfers occurred in air. Six samples were sliced from four pellets elaborated by carbothermic reaction under vacuum. Little presence of UC2 is expected in these samples. The α-UC2 phase was indeed detected within one of these UC samples during an XRD experiment performed with synchrotron radiation. Moreover, oxygen content at the surface of these samples was depth profiled using a recently developed nuclear reaction analysis method. Large oxygen concentrations were measured in the first micron below the sample surface and particularly in the first 100-150 nm. UC2 inclusions were found to be more oxidized than the surrounding matrix. This work points out to the fact that more care must be given at each step of UC fabrication since the material readily reacts with oxygen and moisture. A new glovebox facility using a highly purified atmosphere is currently being built in order to obtain single phase UC samples of better purity.

46 CFR 54.25-7 - Requirement for postweld heat treatment (modifies UCS-56).

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Requirement for postweld heat treatment (modifies UCS-56... ENGINEERING PRESSURE VESSELS Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-7 Requirement for postweld heat treatment (modifies UCS-56). (a) Postweld heat treatment is required for all carbon...

46 CFR 54.25-7 - Requirement for postweld heat treatment (modifies UCS-56).

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Requirement for postweld heat treatment (modifies UCS-56... ENGINEERING PRESSURE VESSELS Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-7 Requirement for postweld heat treatment (modifies UCS-56). (a) Postweld heat treatment is required for all carbon...

46 CFR 54.25-7 - Requirement for postweld heat treatment (modifies UCS-56).

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Requirement for postweld heat treatment (modifies UCS-56... ENGINEERING PRESSURE VESSELS Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-7 Requirement for postweld heat treatment (modifies UCS-56). (a) Postweld heat treatment is required for all carbon...

46 CFR 54.25-7 - Requirement for postweld heat treatment (modifies UCS-56).

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Requirement for postweld heat treatment (modifies UCS-56... ENGINEERING PRESSURE VESSELS Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-7 Requirement for postweld heat treatment (modifies UCS-56). (a) Postweld heat treatment is required for all carbon...

UCS-PROMOVE: The Engineer of the Future

ERIC Educational Resources Information Center

Villas-Boas, V.

2010-01-01

The Universidade de Caxias do Sul (UCS) elaborated the cooperative project called "The engineer of the future", with the objective of promoting science and engineering among high school teachers and students. This project aims to improve the quality of the teaching and to increase the interest of students in technological areas, leading…

Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: A double-blind, randomized study

PubMed Central

Ito, Hiroaki; Iida, Mitsuo; Matsumoto, Takayuki; Suzuki, Yasuo; Sasaki, Hidetaka; Yoshida, Toyomitsu; Takano, Yuichi; Hibi, Toshifumi

2010-01-01

Background: Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC. Methods: In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active UC were assigned to 4 groups: 66 and 65 received a pH-dependent release formulation of 2.4 g/day (pH-2.4 g) or 3.6 g/day (pH-3.6 g), respectively; 65 received a time-dependent release formulation of 2.25 g/day (Time-2.25 g), and 33 received placebo (Placebo). The drugs were administered three times daily for eight weeks. The primary endpoint was a decrease in the UC disease activity index (UC-DAI). Results: In the full analysis set (n = 225) the decrease in UC-DAI in each group was 1.5 in pH-2.4 g, 2.9 in pH-3.6 g, 1.3 in Time-2.25 g and 0.3 in Placebo, respectively. These results demonstrate the superiority of pH-3.6 g over Time-2.25 g (P = 0.003) and the noninferiority of pH-2.4 g to Time-2.25 g. Among the patients with proctitis-type UC, a significant decrease in UC-DAI was observed in pH-2.4 g and pH-3.6 g as compared to Placebo, but not in Time-2.25 g. No differences were observed in the safety profiles. Conclusions: Higher dose of the pH-dependent release formulation was more effective for induction of remission in patients with mild-to-moderate active UC. Additionally, the pH-dependent release formulation was preferable to the time-dependent release formulation for patients with proctitis-type UC (UMIN Clinical Trials Registry, no. C000000288). (Inflamm Bowel Dis 2010) PMID:20049950

Clinical Efficacy and Safety of Oral Qing-Dai in Patients with Ulcerative Colitis: A Single-Center Open-Label Prospective Study.

PubMed

Sugimoto, Shinya; Naganuma, Makoto; Kiyohara, Hiroki; Arai, Mari; Ono, Keiko; Mori, Kiyoto; Saigusa, Keiichiro; Nanki, Kosaku; Takeshita, Kozue; Takeshita, Tatsuya; Mutaguchi, Makoto; Mizuno, Shinta; Bessho, Rieko; Nakazato, Yoshihiro; Hisamatsu, Tadakazu; Inoue, Nagamu; Ogata, Haruhiko; Iwao, Yasushi; Kanai, Takanori

2016-01-01

Chinese herbal medicine Qing-Dai (also known as indigo naturalis) has been used to treat various inflammatory conditions. However, not much has been studied about the use of oral Qing-Dai in the treatment for ulcerative colitis (UC) patients. Studies exploring alternative treatments for UC are of considerable interest. In this study, we aimed at prospectively evaluating the safety and efficacy of Qing-Dai for UC patients. The open-label, prospective pilot study was conducted at Keio University Hospital. A total of 20 patients with moderate UC activity were enrolled. Oral Qing-Dai in capsule form was taken twice a day (daily dose, 2 g) for 8 weeks. At week 8, the rates of clinical response, clinical remission, and mucosal healing were 72, 33, and 61%, respectively. The clinical and endoscopic scores, CRP levels, and fecal occult blood results were also significantly improved. We observed 2 patients with mild liver dysfunction; 1 patient discontinued due to infectious colitis and 1 patient discontinued due to mild nausea. This is the first prospective study indicating that oral Qing-Dai is effective for inducing remission in patients with moderate UC activity and can be tolerated. Thus, Qing-Dai may be considered an alternative treatment for patients, although further investigation is warranted. © 2016 S. Karger AG, Basel.

[The risk factor for low bone mineral density in patients with inflammatory bowel disease].

PubMed

Liu, Jian-bin; Gao, Xiang; Zhang, Fang-bin; Yang, Li; Xiao, Ying-lian; Zhang, Rui-dong; Li, Zi-ping; Hu, Pin-jin; Chen, Min-hu

2009-10-01

To evaluate the prevalence of low bone mineral density in patients with inflammatory bowel disease (IBD)and to identify its risk factors. A cross-sectional survey was carried out in IBD patients. Anthropometric measures, biochemical markers of nutrition and bone mineral density measurement were completed for these patients as well as healthy control subjects. Seventy-seven Crohn's disease (CD) and 43 ulcerative colitis (UC) patients were enrolled, and 37 healthy volunteers were recruited as healthy controls (HC). The T value of CD patients, UC patients and HC was -1.72 +/- 1.20, -1.26 +/- 1.12 and -0.62 +/- 0.87 respectively and the T value of CD patients was significantly lower than that of HC (P = 0.000). The prevalence of osteoporosis in CD, UC and HC was 23.3%, 14.0% and 0 respectively. The prevalence of osteoporosis in CD was higher than that in HC (P = 0.003). Logistic regression analysis indicated that low BMI (BMI < or = 18.4 kg/m(2)) was an independent risk factor for osteoporosis both in CD (OR = 11.25, 95%CI 3.198 - 39.580, P = 0.000) and in UC (OR = 14.50, 95%CI 1.058 - 88.200, P = 0.045) patients. Age, disease duration, clinical activity active index (CDAI), oral steroid therapy, immunosuppressant treatment and serum vitamin D concentration were not found to be correlated with osteoporosis in IBD patients. Low bone mineral density is common in both CD and UC patients and low BMI is an independent risk factor for osteoporosis in IBD patients.

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.

Linking academic and clinical missions: UC Davis' integrated AHC.

PubMed

Pomeroy, Claire; Rice, Ann; McGowan, William; Osburn, Nathan

2008-09-01

Academic health centers (AHCs) rely on cross-subsidization of education and research programs by the clinical enterprise, but this is becoming more challenging as clinical reimbursements decline. These new realities provide an important opportunity to reevaluate the relationships between medical schools and academic medical centers. The authors examine the benefits of their ongoing commitment to create a fully integrated AHC at the University of California (UC) Davis, discussing strategies that serve as catalysts for continued growth. They explore how investments of proceeds from the clinical enterprise directly enhance educational and research initiatives, which, in turn, increase the success of patient-care programs. This has created a cycle of excellence that leads to an enhanced reputation for the entire health system. One strategy involves using clinical margins to "prime the pump" in anticipation of major research initiatives, resulting in rapid increases in external research funding and academic recognition. In turn, this facilitates recruitment of high-quality faculty and staff, improving the ability to deliver expert clinical care. The overall enhanced institutional reputation positions both the clinical and academic programs for further success. The authors posit that such approaches require executive-level commitment to a single strategic vision, unified leadership, and collaborative financial and operational decision making. Adopting such changes is not without challenges, which are discussed, but the authors suggest that an integrated AHC fosters optimized operations, enhanced reputation, and stronger performance across all mission areas. They also provide examples of how the UC Davis Health System has thus attracted philanthropists and investments from the private sector.

Salmon diet in patients with active ulcerative colitis reduced the simple clinical colitis activity index and increased the anti-inflammatory fatty acid index--a pilot study.

PubMed

Grimstad, Tore; Berge, Rolf K; Bohov, Pavol; Skorve, Jon; Gøransson, Lasse; Omdal, Roald; Aasprong, Ole G; Haugen, Margaretha; Meltzer, Helle M; Hausken, Trygve

2011-02-01

Data concerning the anti-inflammatory effect of dietary n-3 polyunsaturated fatty acids (PUFAs) in patients with ulcerative colitis (UC) are inconsistent. Salmon fillet contains n-3 PUFAs and bioactive peptides that may improve its effects compared to fish oil alone. We assessed the efficacy of a salmon-rich diet in patients with mild ulcerative colitis. An 8-week intervention pilot study was designed to assess the effects of 600 grams Atlantic salmon consumption weekly in 12 UC patients. Simple clinical colitis activity index (SCCAI), a dietary questionnaire, sigmoidoscopy, selected serum inflammatory markers, fecal calprotectin, and plasma and rectal biopsy fatty acid profiles were assessed before and after intervention. The levels of C20:4n-6 arachidonic acid in biopsies after dietary intervention were correlated with histology and endoscopy scores. The concentrations of n-3 PUFAs, C20:5n-3 eicosapentaenoic acid, C22:6n-3 docosahexaenoic acid, and the n-3/n-6 ratio increased in plasma and rectal biopsies. The anti-inflammatory fatty acid index (AIFAI) increased both in biopsies and plasma accompanied with a significantly reduced SCCAI. Based on evidence of SCCAI and AIFAI and a tendency of decreased levels of CRP and homocysteine, intake of Atlantic salmon may have beneficial effects on disease activity in patients with mild ulcerative colitis.

Oxidation of UC: An in situ high temperature environmental scanning electron microscopy study

NASA Astrophysics Data System (ADS)

Gasparrini, Claudia; Podor, Renaud; Horlait, Denis; Rushton, Michael J. D.; Fiquet, Olivier; Lee, William Edward

2017-10-01

In situ HT-ESEM oxidation of sintered UC fragments revealed the morphological changes occurring during the transformation between UC to UO2 and UO2 to U3O8 at 723-848 K and in an atmosphere of 10-100 Pa O2. Two main oxidation pathways were revealed. Oxidation at 723 K in atmospheres ≤25 Pa O2 showed the transformation from UC to UO2+x, as confirmed by post mortem HRTEM analysis. This oxidation pathway was comprised of three steps: (i) an induction period, where only surface UC particles oxidised, (ii) a sample area expansion accompanied by crack formation and propagation, (iii) a stabilisation of the total crack length inferring that crack propagation had stopped. Samples oxidised under 50 Pa O2 at 723 K and at 773-848 K for 10-100 Pa O2 showed an "explosive" oxidation pathway: (i) sample area expansion occurred as soon as oxygen was inserted into the chamber and crack propagation and crack length followed an exponential law; (ii) cracks propagated as a network and the oxide layer fragmented, (iii) an "explosion" occurred causing a popcorn-like transformation, typical for oxidation from UO2 to U3O8. HRTEM characterisation revealed U3O8 preferentially grow in the [001] direction. The explosive growth, triggered by ignition of UC, proceeded as a self-propagating high-temperature synthesis reaction, with a propagation speed of 150-500 ± 50 μm/s.

Combination of corticosteroids and 5-aminosalicylates or corticosteroids alone for patients with moderate-severe active ulcerative colitis: A global survey of physicians' practice.

PubMed

Ben-Horin, Shomron; Andrews, Jane M; Katsanos, Konstantinos H; Rieder, Florian; Steinwurz, Flavio; Karmiris, Konstantinos; Cheon, Jae Hee; Moran, Gordon William; Cesarini, Monica; Stone, Christian D; Schwartz, Doron; Protic, Marijana; Roblin, Xavier; Roda, Giulia; Chen, Min-Hu; Har-Noy, Ofir; Bernstein, Charles N

2017-04-28

To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates (5ASA) with corticosteroids (CS) versus corticosteroids alone for patients with active ulcerative colitis (UC). A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents' agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses. Six hundred and sixty-four questionnaires were distributed and 349 received (52.6% response rate). Of 340 eligible respondents, 221 (65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108 (32%) would stop the 5ASA ( P < 0.001), and 11 (3%) are undecided. Similarly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340 (41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most (94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS. Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients.

A transcribed ultraconserved noncoding RNA, Uc.173, is a key molecule for the inhibition of lead-induced neuronal apoptosis

PubMed Central

Chen, Lijian; Liu, Meiling; Zhang, Nan; Zhang, Li; Luo, Yuanwei; Liu, Zhenzhong; Dai, Lijun; Jiang, Yiguo

2016-01-01

As a common toxic metal, lead has significant neurotoxicity to brain development. Long non-coding RNAs (lncRNAs) function in multiple biological processes. However, whether lncRNAs are involved in lead-induced neurotoxicity remains unclear. Uc.173 is a lncRNA from a transcribed ultra-conservative region (T-UCR) of human, mouse and rat genomes. We established a lead-induced nerve injury mouse model. It showed the levels of Uc.173 decreased significantly in hippocampus tissue and serum of the model. We further tested the expression of Uc.173 in serum of lead-exposed children, which also showed a tendency to decrease. To explore the effects of Uc.173 on lead-induced nerve injury, we overexpressed Uc.173 in an N2a mouse nerve cell line and found Uc.173 had an inhibitory effect on lead-induced apoptosis of N2a. To investigate the molecular mechanisms of Uc.173 in apoptosis associated with lead-induced nerve injury, we predicted the target microRNAs of Uc.173 by using miRanda, TargetScan and RegRNA. After performing quantitative real-time PCR and bioinformatics analysis, we showed Uc.173 might inter-regulate with miR-291a-3p in lead-induced apoptosis and regulate apoptosis-associated genes. Our study suggests Uc.173 significantly inhibits the apoptosis of nerve cells, which may be mediated by inter-regulation with miRNAs in lead-induced nerve injury. PMID:26683706

Safety and Efficacy of Combination Treatment With Calcineurin Inhibitors and Vedolizumab in Patients With Refractory Inflammatory Bowel Disease.

PubMed

Christensen, Britt; Gibson, Peter; Micic, Dejan; Colman, Ruben J; Goeppinger, Sarah R; Kassim, Olufemmi; Yarur, Andres; Weber, Christopher R; Cohen, Russell D; Rubin, David T

2018-05-08

Little is known about the efficacy and safety of induction therapy with calcineurin inhibitors in combination with vedolizumab for patients with Crohn's disease (CD) or ulcerative colitis (UC). We analyzed the outcomes of patients receiving vedolizumab along with calcineurin inhibitors METHODS: We collected data on patients with CD (n=9) or UC (n=11) who began treatment with vedolizumab from May 20, 2014 through March 30, 2015 and received calcineurin inhibitors (tacrolimus or cyclosporin) during the first 12 months of vedolizumab therapy. Clinical activity scores and inflammatory markers were measured at baseline and at weeks 14, 30, and 52 of vedolizumab treatment. Clinical remission was defined as a Harvey Bradshaw index score ≤4 or short clinical colitis activity index score ≤2; steroid-free clinical remission was defined as clinical remission without corticosteroids. By week 14 of treatment, 44% of the patients with CD and 55% of the patients with UC achieved steroid-free clinical remission; after 52 weeks of treatment, 33% of the patients with CD and 45% of the patients with UC were in steroid-free clinical remission. Seven patients received salvage therapy with a calcineurin inhibitor after primary non-response to vedolizumab-1 of the 2 patients with UC and 2 of 5 patients with CD stopped taking the calcineurin inhibitors and achieved steroid-free remission at week 52. In total, 16 patients (59%) received 52 weeks of treatment with vedolizumab. Three serious adverse events were associated with calcineurin inhibitors. Combination therapy of vedolizumab with either cyclosporin or tacrolimus is effective and safe at inducing and maintaining clinical remission in patients with CD and UC with up to 52 weeks of follow-up. Larger studies of the ability of calcineurin inhibitors to induce remission in patients on vedolizumab are warranted. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Theoretical study of actinide monocarbides (ThC, UC, PuC, and AmC)

NASA Astrophysics Data System (ADS)

Pogány, Peter; Kovács, Attila; Visscher, Lucas; Konings, Rudy J. M.

2016-12-01

A study of four representative actinide monocarbides, ThC, UC, PuC, and AmC, has been performed with relativistic quantum chemical calculations. The two applied methods were multireference complete active space second-order perturbation theory (CASPT2) including the Douglas-Kroll-Hess Hamiltonian with all-electron basis sets and density functional theory with the B3LYP exchange-correlation functional in conjunction with relativistic pseudopotentials. Beside the ground electronic states, the excited states up to 17 000 cm-1 have been determined. The molecular properties explored included the ground-state geometries, bonding properties, and the electronic absorption spectra. According to the occupation of the bonding orbitals, the calculated electronic states were classified into three groups, each leading to a characteristic bond distance range for the equilibrium geometry. The ground states of ThC, UC, and PuC have two doubly occupied π orbitals resulting in short bond distances between 1.8 and 2.0 Å, whereas the ground state of AmC has significant occupation of the antibonding orbitals, causing a bond distance of 2.15 Å.

IBS-like Symptoms in Patients with Ulcerative Colitis in Deep Remission Are Associated with Increased Levels of Serum Cytokines and Poor Psychological Well-being.

PubMed

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

2016-11-01

Gastrointestinal symptoms (GI) compatible with irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in remission. The causes of these symptoms remain to be clarified. Our aim was to investigate prevalence and factors associated with IBS-like symptoms in patients with UC in deep remission. We included 298 patients with UC and used Mayo score, sigmoidoscopy, and fecal calprotectin to define deep remission versus active disease. Presence of IBS-like symptoms according to the Rome III criteria, severity of GI, extraintestinal and psychological symptoms, stress levels, and quality of life were measured with validated questionnaires. Serum cytokines and high-sensitive C-reactive peptide were determined. The criteria for deep remission was fulfilled by 132 patients (44%) and 24 of these fulfilled the Rome III criteria for IBS (18%). Patients with UC in deep remission with IBS-like symptoms had comparable levels of GI symptoms, non-GI somatic symptoms, and quality of life as patients with active UC. The patients with UC in deep remission with IBS-like symptoms had similar levels of fecal calprotectin as patients in deep remission without IBS-like symptoms (18 versus 31 μg/g, P = 0.11), but higher levels of serum cytokines (interleukin [IL]-1β, IL-6, IL-13, IL-10 and IL-8, P < 0.05) and higher levels of anxiety (P < 0.001), depression (P = 0.02) and perceived stress (P = 0.03). IBS-like symptoms in patients with UC in deep remission are common, but not as prevalent as previously reported. Poor psychological well-being and increased serum cytokine levels, but not colonic low-grade inflammation, were associated with IBS-like symptoms.

Systematic review with meta-analysis: real-world effectiveness and safety of vedolizumab in patients with inflammatory bowel disease.

PubMed

Schreiber, Stefan; Dignass, Axel; Peyrin-Biroulet, Laurent; Hather, Greg; Demuth, Dirk; Mosli, Mahmoud; Curtis, Rebecca; Khalid, Javaria Mona; Loftus, Edward Vincent

2018-06-04

Selective patient recruitment can produce discrepancies between clinical trial results and real-world effectiveness. A systematic literature review and meta-analysis were conducted to assess vedolizumab real-world effectiveness and safety in patients with ulcerative colitis (UC) or Crohn's disease (CD). MEDLINE, MEDLINE In-Process, EMBASE, and Cochrane databases were searched for real-world studies of vedolizumab in adult patients with UC/CD reporting clinical response, remission, corticosteroid-free remission, UC/CD-related surgery or hospitalization, mucosal healing, or safety published from May 1, 2014-June 22, 2017. Response and remission rates were combined in random-effects meta-analyses. At treatment week 14, 32% of UC patients [95% confidence interval (CI) 27-39%] and 30% of CD patients (95% CI 25-34%) were in remission; and at month 12, 46% for UC (95% CI 37-56%) and 30% for CD (95% CI 20-42%). For UC, the rates of corticosteroid-free remission were 26% at week 14 (95% CI 20-34%) and 42% at month 12 (95% CI 31-53%); for CD they were 25% at week 14 (95%, CI 20-31%) and 31% at month 12 (95%, CI 20-45%). At month 12, 33-77% of UC and 6-63% of CD patients had mucosal healing. Nine percent of patients reported serious adverse events. Vedolizumab demonstrated real-world effectiveness in patients with moderate-to-severely active UC or CD, with approximately one-half and one-third of patients, respectively, in remission at treatment month 12. These findings are consistent with clinical trial data and support the long-term benefit-risk profile of vedolizumab.

Gene expression profile of endoscopically active and inactive ulcerative colitis: preliminary data.

PubMed

Ţieranu, Cristian George; Dobre, Maria; Mănuc, Teodora Ecaterina; Milanesi, Elena; Pleşea, Iancu Emil; Popa, Caterina; Mănuc, Mircea; Ţieranu, Ioana; Preda, Carmen Monica; Diculescu, Mihai Mircea; Ionescu, Elena Mirela; Becheanu, Gabriel

2017-01-01

Multiple cytokines and chemokines related to immune response, apoptosis and inflammation have been identified as molecules implicated in ulcerative colitis (UC) pathogenesis. The aim of this study was to identify the differences at gene expression level of a panel of candidate genes in mucosa from patients with active UC (UCA), patients in remission (UCR), and normal controls. Eleven individuals were enrolled in the study: eight UC patients (four with active lesions, four with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression profile was evaluated by polymerase chain reaction (PCR) array, investigating 84 genes implicated in apoptosis, inflammation, immune response, cellular adhesion, tissue remodeling and mucous secretion. Seventeen and three genes out of 84 were found significantly differentially expressed in UCA and UCR compared to controls, respectively. In particular, REG1A and CHI3L1 genes reported an up-regulation in UCA with a fold difference above 200. In UCR patients, the levels of CASP1, LYZ and ISG15 were different compared to controls. However, since a significant up-regulation of both CASP1 and LYZ was observed also in the UCA group, only ISG15 levels remained associated to the remission state. ISG15, that plays a key role in the innate immune response, seemed to be specifically associated to the UC remission state. These preliminary data represent a starting point for defining the gene profile of UC in different stages in Romanian population. Identification of genes implicated in UC pathogenesis could be useful to select new therapeutic targets.

Altered STAT4 Isoform Expression in Patients with Inflammatory Bowel Disease.

PubMed

Jabeen, Rukhsana; Miller, Lucy; Yao, Weiguo; Gupta, Sandeep; Steiner, Steven; Kaplan, Mark H

2015-10-01

Crohn's disease (CD) and ulcerative colitis (UC) are the major forms of inflammatory bowel disease, and pathogenesis involves a complex interplay among genetic, environmental, and immunological factors. We evaluated isoform expression of the IL-12-activated transcription factor STAT4 in children with CD and UC. We collected biopsy samples from both patients newly diagnosed with CD and with UC. We further collected blood samples from patients newly diagnosed with CD and with UC as well as from patients who had a flare-up after being in clinical remission, and we examined the ratios of STAT4β/STAT4α mRNA. In addition to STAT4 isoforms, we measured the expression of the cytokines TNFα, IFNγ, granulocyte macrophage-colony stimulating factor, and IL-17 using polymerase chain reaction of biopsy samples and multiplex analysis of patient serum samples. Ratios of STAT4β/STAT4α were increased in specific gastrointestinal tract segments in both patients with CD and those with UC that correlate with the location and severity of inflammation. In contrast, we did not observe changes in STAT4β/STAT4α ratios in biopsy specimens from patients with eosinophilic esophagitis. We also observed increased STAT4β/STAT4α ratios in the peripheral blood mononuclear cells of patients with UC and those with CD, compared with healthy controls. Ratios were normalized after patients were treated with steroids. Collectively, these data indicate that STAT4 isoforms could be an important noninvasive biomarker in the diagnosis and treatment of inflammatory bowel disease and that expression of these isoforms might provide further insight into the pathogenesis of IBD.

Primary Care Provider Perceptions of the Effectiveness of Two Self-Management Support Programs for Vulnerable Patients with Diabetes

PubMed Central

Ratanawongsa, Neda; Bhandari, Vijay K; Handley, Margaret; Rundall, Thomas; Hammer, Hali; Schillinger, Dean

2012-01-01

Background Primary care providers (PCPs) in safety net settings face barriers to optimizing care for patients with diabetes. We conducted this study to assess PCPs' perspectives on the effectiveness of two language-concordant diabetes self-management support programs. Methods One year postintervention, we surveyed PCPs whose patients with diabetes participated in a three-arm multiclinic randomized controlled trial comparing usual care (UC), weekly automated telephone self-management (ATSM) support with nurse care management, and monthly group medical visits (GMVs). We compared PCP perspectives on patient activation to create and achieve goals, quality of care, and barriers to care using regression models accounting for within-PCP clustering. Results Of 113 eligible PCPs caring for 330 enrolled patients, 87 PCPs (77%) responded to surveys about 245 (74%) enrolled patients. Intervention patients were more likely to be perceived by PCPs as activated to create and achieve goals for chronic care when compared with UC patients (standardized effect size, ATSM vs UC, +0.41, p = 0.01; GMV vs UC, +0.31, p = 0.05). Primary care providers rated quality of care as higher for patients exposed to ATSM compared to UC (odds ratio 3.6, p < 0.01). Compared with GMV patients, ATSM patients were more likely to be perceived by PCPs as overcoming barriers related to limited English proficiency (82% ATSM vs 44% GMV, p = 0.01) and managing medications (80% ATSM vs 53% GMV, p = 0.01). Conclusions Primary care providers perceived that patients receiving ATSM support had overcome barriers, participated more actively, and received higher quality diabetes care. These views of clinician stakeholders lend additional evidence for the potential to upscale ATSM more broadly to support PCPs in their care of diverse, multilinguistic populations. PMID:22401329

Randomized, placebo-controlled trial of low molecular weight heparin in active ulcerative colitis.

PubMed

de Bièvre, M A; Vrij, A A; Schoon, E J; Dijkstra, G; de Jong, A E; Oberndorff-Klein Woolthuis, A H; Hemker, H C; Stockbrügger, R W

2007-06-01

In several open and 1 controlled trial, unfractionated heparin was effective in the treatment of active ulcerative colitis (UC). Low molecular weight heparin (LMWH) had a similar effect in several open studies. We studied the efficacy, safety, and tolerability of LMWH in mild to moderately active UC in a randomized, double-blind, placebo-controlled trial. In all, 29 patients with a mild or moderate recurrence of UC during salicylate treatment were randomized to receive either reviparin 3,436 IU (n = 15) subcutaneously twice daily or placebo (n = 14). The study period was 8 weeks. Treatment was discontinued if there was no improvement at 4 weeks or at any disease progression. Primary outcome measure was clinical improvement at 8 weeks measured by the Colitis Activity Index (CAI) and the Clinical Symptoms Grading (CSG, based on the CAI). Endoscopic and histologic grading and quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) were secondary outcome measures. Patients were closely monitored for adverse events. Twenty of 29 patients finished the 8-week treatment period (reviparin versus placebo: 11 versus 9; P = 0.70). There was no difference in CSG, CAI, endoscopic and histologic grading, or IBDQ. Treatment was well tolerated and no serious adverse events occurred. In this study, treatment with LMWH showed no significant clinical advantage compared to placebo in mild to moderately active UC.

Successful Use of Tocilizumab in a Patient with Coexisting Rheumatoid Arthritis and Ulcerative Colitis.

PubMed

Szeto, Matthew Chak Hin; Yalçın, Metin Devrim; Khan, Abdul; Piotrowicz, Andrzej

2016-01-01

Tocilizumab is an interleukin-6 receptor inhibitor licensed for moderate to severe rheumatoid arthritis (RA). We report a case of Tocilizumab monotherapy for severe active RA in a patient with coexisting ulcerative colitis (UC). The patient was intolerant to multiple disease-modifying drugs, so Tocilizumab monotherapy was commenced. We found clinical improvement in both RA and UC. There was no major adverse event after 2 years. Manufacturer advised caution in using Tocilizumab in patient with gastrointestinal ulceration due to an increased risk of bowel perforation. However, alternative treatments such as glucocorticoid and nonsteroidal anti-inflammatory drugs may carry a higher bowel perforation risk. The presence of gastrointestinal ulceration therefore should not constitute an absolute contraindication for Tocilizumab therapy. Future studies of registry data will inform clinician of the Tocilizumab-related risk of gastrointestinal toxicity in "real-life" settings. Contrary to previous case report, we found Tocilizumab therapy to have a positive effect on UC. Laboratory studies supported a role for interleukin-6 in the pathophysiology of UC. Further clinical trial to evaluate the therapeutic role of Tocilizumab in UC would be warranted.

Quantification of process variables for carbothermic synthesis of UC 1-xN x fuel microspheres

DOE PAGES

Lindemer, Terrance B.; Silva, Chinthaka M.; Henry, Jr, John James; ...

2016-11-05

This report details the continued investigation of process variables involved in converting sol-gel-derived, urania-carbon microspheres to ~820-μm-dia. UC 1-xN x fuel kernels in flow-through, vertical Mo and W crucibles at temperatures up to 2123 K. Experiments included calcining of air-dried UO 3-H 2O-C microspheres in Ar and H 2-containing gases, conversion of the resulting UO 2-C kernels to dense UO2:2UC in the same gases and vacuum, and its conversion in N 2 to UC 1-xN x (x = ~0.85). The thermodynamics of the relevant reactions were applied extensively to interpret and control the process variables. Producing the precursor UO 2:2UCmore » kernel of ~96% theoretical density was required, but its subsequent conversion to UC 1-xN x at 2123 K was not accompanied by sintering and resulted in ~83-86% of theoretical density. Increasing the UC 1-xN x kernel nitride component to ~0.98 in flowing N 2-H 2 mixtures to evolve HCN was shown to be quantitatively consistent with present and past experiments and the only useful application of H 2 in the entire process.« less

Human Mesenchymal Stem Cell Transfusion Is Safe and Improves Liver Function in Acute-on-Chronic Liver Failure Patients

PubMed Central

Shi, Ming; Zhang, Zheng; Xu, Ruonan; Lin, Hu; Fu, Junliang; Zou, Zhengsheng; Zhang, Aimin; Shi, Jianfei; Chen, Liming; Lv, Sa; He, Weiping; Geng, Hua; Jin, Lei; Liu, Zhenwen

2012-01-01

Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cord-derived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients. PMID:23197664

{sup 1}H NMR-based spectroscopy detects metabolic alterations in serum of patients with early-stage ulcerative colitis

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

Zhang, Ying; Lin, Lianjie; Xu, Yanbin

2013-04-19

Highlights: •Twenty ulcerative colitis patients and nineteen healthy controls were enrolled. •Increased 3-hydroxybutyrate, glucose, phenylalanine, and decreased lipid were found. •We report early stage diagnosis of ulcerative colitis using NMR-based metabolomics. -- Abstract: Ulcerative colitis (UC) has seriously impaired the health of citizens. Accurate diagnosis of UC at an early stage is crucial to improve the efficiency of treatment and prognosis. In this study, proton nuclear magnetic resonance ({sup 1}H NMR)-based metabolomic analysis was performed on serum samples collected from active UC patients (n = 20) and healthy controls (n = 19), respectively. The obtained spectral profiles were subjected tomore » multivariate data analysis. Our results showed that consistent metabolic alterations were present between the two groups. Compared to healthy controls, UC patients displayed increased 3-hydroxybutyrate, β-glucose, α-glucose, and phenylalanine, but decreased lipid in serum. These findings highlight the possibilities of NMR-based metabolomics as a non-invasive diagnostic tool for UC.« less

The UC2-x - Carbon eutectic: A laser heating study

NASA Astrophysics Data System (ADS)

Manara, D.; Boboridis, K.; Morel, S.; De Bruycker, F.

2015-11-01

The UC2-x - carbon eutectic has been studied by laser heating and fast multi-wavelength pyrometry under inert atmosphere. The study has been carried out on three compositions, two of which close to the phase boundary of the UC2-x - C miscibility gap (with C/U atomic ratios 2 and 2.1), and one, more crucial, with a large excess of carbon (C/U = 2.82). The first two compositions were synthesised by arc-melting. This synthesis method could not be applied to the last composition, which was therefore completed directly by laser irradiation. The U - C - O composition of the samples was checked by using a combustion method in an ELTRA® analyser. The eutectic temperature, established to be 2737 K ± 20 K, was used as a radiance reference together with the cubic - tetragonal (α → β) solid state transition, fixed at 2050 K ± 20 K. The normal spectral emissivity of the carbon-richer compounds increases up to 0.7, whereas the value 0.53 was established for pure hypostoichiometric uranium dicarbide at the limit of the eutectic region. This increase is analysed in the light of the demixing of excess carbon, and used for the determination of the liquidus temperature (3220 K ± 50 K for UC2.82). Due to fast solid state diffusion, also fostered by the cubic - tetragonal transition, no obvious signs of a lamellar eutectic structure could be observed after quenching to room temperature. The eutectic surface C/UC2-x composition could be qualitatively, but consistently, followed during the cooling process with the help of the recorded radiance spectra. Whereas the external liquid surface is almost entirely constituted by uranium dicarbide, it gets rapidly enriched in demixed carbon upon freezing. Demixed carbon seems to quickly migrate towards the inner bulk during further cooling. At the α → β transition, uranium dicarbide covers again the almost entire external surface.

Individual health discount rate in patients with ulcerative colitis.

PubMed

Waljee, Akbar K; Morris, Arden M; Waljee, Jennifer F; Higgins, Peter D R

2011-06-01

In cost-effectiveness analysis, discount rates are used in calculating the value of future costs and benefits. However, standard discount rates may not accurately describe the decision-making of patients with ulcerative colitis (UC). These patients often choose the long-term risks of immunosuppressive therapy over the short-term risks of colectomy, demonstrating very high discount rates for future health. In this study we aimed to measure the discount rate in UC patients and identify variables associated with the discount rate. We surveyed patients with UC and patients who were postcolectomy for UC to measure their valuations of UC and colectomy health states. We used Standard Gamble (SG) and Time-Trade-Off (TTO) methods to assess current and future health state valuations and calculated the discount rate. Participants included 150 subjects with UC and 150 subjects who were postcolectomy for UC. Adjusted discount rates varied widely (0%-100%), with an overall median rate of 55.0% (interquartile range [IQR] 20.6-100), which was significantly higher than the standard rate of 5%. Within the normal range of discount rates, patients' expected discount rate increased by 0.80% for each additional year of age, and female patients had discount rates that averaged ≈ 8% less than their age-matched counterparts and approached statistical significance. The accepted discount rate of 5% grossly underestimates UC patients' preference for long-term over short-term risk. This might explain UC patients' frequent choice of the long-term risks of immunosuppressive medical therapy over the short-term risks of colectomy. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

Molecular insight on the non-covalent interactions between carbapenems and uc(l,d)-transpeptidase 2 from Mycobacterium tuberculosis: ONIOM study

NASA Astrophysics Data System (ADS)

Ntombela, Thandokuhle; Fakhar, Zeynab; Ibeji, Collins U.; Govender, Thavendran; Maguire, Glenn E. M.; Lamichhane, Gyanu; Kruger, Hendrik G.; Honarparvar, Bahareh

2018-05-01

Tuberculosis remains a dreadful disease that has claimed many human lives worldwide and elimination of the causative agent Mycobacterium tuberculosis also remains elusive. Multidrug-resistant TB is rapidly increasing worldwide; therefore, there is an urgent need for improving the current antibiotics and novel drug targets to successfully curb the TB burden. uc(l,d)-Transpeptidase 2 is an essential protein in Mtb that is responsible for virulence and growth during the chronic stage of the disease. Both uc(d,d)- and uc(l,d)-transpeptidases are inhibited concurrently to eradicate the bacterium. It was recently discovered that classic penicillins only inhibit uc(d,d)-transpeptidases, while uc(l,d)-transpeptidases are blocked by carbapenems. This has contributed to drug resistance and persistence of tuberculosis. Herein, a hybrid two-layered ONIOM (B3LYP/6-31G+(d): AMBER) model was used to extensively investigate the binding interactions of LdtMt2 complexed with four carbapenems (biapenem, imipenem, meropenem, and tebipenem) to ascertain molecular insight of the drug-enzyme complexation event. In the studied complexes, the carbapenems together with catalytic triad active site residues of LdtMt2 (His187, Ser188 and Cys205) were treated at with QM [B3LYP/6-31+G(d)], while the remaining part of the complexes were treated at MM level (AMBER force field). The resulting Gibbs free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) for all complexes showed that the carbapenems exhibit reasonable binding interactions towards LdtMt2. Increasing the number of amino acid residues that form hydrogen bond interactions in the QM layer showed significant impact in binding interaction energy differences and the stabilities of the carbapenems inside the active pocket of LdtMt2. The theoretical binding free energies obtained in this study reflect the same trend of the experimental observations. The electrostatic, hydrogen bonding and Van der Waals interactions between the carbapenems and Ldt

Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease.

PubMed

Rosario, M; Dirks, N L; Gastonguay, M R; Fasanmade, A A; Wyant, T; Parikh, A; Sandborn, W J; Feagan, B G; Reinisch, W; Fox, I

2015-07-01

Vedolizumab, an anti-α(4)β(7) integrin monoclonal antibody (mAb), is indicated for treating patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). As higher therapeutic mAb concentrations have been associated with greater efficacy in inflammatory bowel disease, understanding determinants of vedolizumab clearance may help to optimise dosing. To characterise vedolizumab pharmacokinetics in patients with UC and CD, to identify clinically relevant determinants of vedolizumab clearance, and to describe the pharmacokinetic-pharmacodynamic relationship using population modelling. Data from a phase 1 healthy volunteer study, a phase 2 UC study, and 3 phase 3 UC/CD studies were included. Population pharmacokinetic analysis for repeated measures was conducted using nonlinear mixed effects modelling. Results from the base model, developed using extensive phase 1 and 2 data, were used to develop the full covariate model, which was fit to sparse phase 3 data. Vedolizumab pharmacokinetics was described by a 2-compartment model with parallel linear and nonlinear elimination. Using reference covariate values, linear elimination half-life of vedolizumab was 25.5 days; linear clearance (CL(L)) was 0.159 L/day for UC and 0.155 L/day for CD; central compartment volume of distribution (V(c)) was 3.19 L; and peripheral compartment volume of distribution was 1.66 L. Interindividual variabilities (%CV) were 35% for CLL and 19% for V(c); residual variance was 24%. Only extreme albumin and body weight values were identified as potential clinically important predictors of CL(L). Population pharmacokinetic parameters were similar in patients with moderately to severely active UC and CD. This analysis supports use of vedolizumab fixed dosing in these patients. Clinicaltrials.gov Identifiers: NCT01177228; NCT00783718 (GEMINI 1); NCT00783692 (GEMINI 2); NCT01224171 (GEMINI 3). © 2015 Takeda Pharmaceuticals International Co published by John Wiley & Sons

Treatment of Ischemia-Reperfusion Injury of the Skin Flap Using Human Umbilical Cord Mesenchymal Stem Cells (hUC-MSCs) Transfected with "F-5" Gene.

PubMed

Leng, Xiangfeng; Fan, Yongle; Wang, Yating; Sun, Jian; Cai, Xia; Hu, Chunnan; Ding, Xiaoying; Hu, Xiaoying; Chen, Zhengyu

2017-06-06

BACKGROUND Recent studies have shown that skin flap transplantation technique plays an important role in surgical procedures. However, there are many problems in the process of skin flap transplantation surgeries, especially ischemia-reperfusion injury, which directly affects the survival rate of the skin flap and patient prognosis after surgeries. MATERIAL AND METHODS In this study, we used a new method of the "stem cells-gene" combination therapy. The "F-5" gene fragment of heat shock protein 90-α (Hsp90-α) was transfected into human umbilical cord mesenchymal stem cells (hUC-MSCs) by genetic engineering technique. RESULTS The synergistic effects of "F-5" gene and hUC-MSCs in the treatment of ischemia-reperfusion injury of the skin flap were confirmed by histochemical and immunohistochemical methods. CONCLUSIONS This study showed that the hUC-MSCs transfected with "F-5" gene can effectively improve the repair of ischemia-reperfusion injury.

A new rapid quantitative test for fecal calprotectin predicts endoscopic activity in ulcerative colitis.

PubMed

Lobatón, Triana; Rodríguez-Moranta, Francisco; Lopez, Alicia; Sánchez, Elena; Rodríguez-Alonso, Lorena; Guardiola, Jordi

2013-04-01

Fecal calprotectin (FC) determined by the enzyme-linked immunosorbent assay (ELISA) test has been proposed as a promising biomarker of endoscopic activity in ulcerative colitis (UC). However, data on its accuracy in predicting endoscopic activity is scarce. Besides, FC determined by the quantitative-point-of-care test (FC-QPOCT) that provides rapid and individual results could optimize its use in clinical practice. The aims of our study were to evaluate the ability of FC to predict endoscopic activity according to the Mayo score in patients with UC when determined by FC-QPOCT and to compare it with the ELISA test (FC-ELISA). FC was determined simultaneously by FC-ELISA and FC-QPOCT in patients with UC undergoing colonoscopy. Clinical disease activity and endoscopy were assessed according to the Mayo score. Blood tests were taken to analyze serological biomarkers. A total of 146 colonoscopies were performed on 123 patients with UC. FC-QPOCT correlated more closely with the Mayo endoscopic subscore (Spearman's correlation coefficient rank r = 0.727, P < 0.001) than clinical activity (r = 0.636, P < 0.001), platelets (r = 0.381, P < 0.001), leucocytes (r = 0.300, P < 0.001), and C-reactive protein (r = 0.291, P = 0.002). The prediction of "endoscopic remission" (Mayo endoscopic subscore ≤1) with FC-QPOCT (280 µg/g) and FC-ELISA (250 µg/g) presented an area under the curve of 0.906 and 0.924, respectively. The interclass correlation index between both tests was 0.904 (95% confidence interval, 0.864-0.932; P < 0.001). FC determined by QPOCT was an accurate surrogate marker of "endoscopic remission" in UC and presented a good correlation with the FC-ELISA test.

Inflammatory bowel disease: a patient's and caregiver's perspective.

PubMed

Magro, F; Portela, F; Lago, P; Deus, J; Cotter, J; Cremers, I; Vieira, A; Peixe, P; Caldeira, P; Lopes, H; Gonçalves, R; Reis, J; Cravo, M; Barros, L; Ministro, P; Lurdes Tavares, M; Duarte, A; Campos, M; Carvalho, L

2009-12-01

The purpose of this study was to conduct a survey examining the impact of inflammatory bowel disease (IBD) on patients' and their caregivers' daily activities. Questionnaires were distributed to patients registered in the APDI (Portuguese Association for IBD) database and their respective caregivers in 2007. Of 422 patient respondents, 251 had Crohn's disease (CD) and 171 had ulcerative colitis (UC), with the majority of patients being women (58.1%) and aged over 40 years (37.4%). The number of disease flares experienced by IBD patients was slightly higher for patients with CD than for patients with UC (2.64 vs. 2.34), and surgery was more often required in CD patients as compared to UC patients (42.4 vs. 7%). Sixty percent (60%) of patients reported having no problems with mobility, daily activities, or personal hygiene; however, over half of all patients experienced some pain and anxiety. Adult patients and children and adolescents respectively experienced time off work or school due to their disease but caregivers were not affected in this regard. The caregivers life (N=324) was affected by anxiety, with the major concern reported as the risk of the patient developing cancer. Both IBD patients and caregivers thought that the provision of information on new drugs and contact time with a doctor would have the biggest impact on improving care. The symptoms and complications of IBD have a considerable impact on the lives of patients and their caregivers, and several actions could be taken to improve their care. © Springer Science+Business Media, LLC 2009

Curcumin in Combination With Mesalamine Induces Remission in Patients With Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled Trial.

PubMed

Lang, Alon; Salomon, Nir; Wu, Justin C Y; Kopylov, Uri; Lahat, Adi; Har-Noy, Ofir; Ching, Jessica Y L; Cheong, Pui Kuan; Avidan, Benjamin; Gamus, Dorit; Kaimakliotis, Ioannis; Eliakim, Rami; Ng, Siew C; Ben-Horin, Shomron

2015-08-01

The phytochemical compound curcumin was reported to be effective in maintaining remission in patients with ulcerative colitis (UC). We investigated curcumin's efficacy in inducing remission in patients with active mild-to-moderate UC. We performed a multicenter randomized, placebo-controlled, double-blind study of 50 mesalamine-treated patients with active mild-to-moderate UC (defined by the Simple Clinical Colitis Activity Index [SCCAI]) who did not respond to an additional 2 weeks of the maximum dose of mesalamine oral and topical therapy. Patients were randomly assigned to groups who were given curcumin capsules (3 g/day, n = 26) or an identical placebo (n = 24) for 1 month, with continued mesalamine. The primary outcome was the rate of clinical remission (SCCAI ≤2) at week 4. Clinical and endoscopic responses were also recorded. In the intention-to-treat analysis, 14 patients (53.8%) receiving curcumin achieved clinical remission at week 4, compared with none of the patients receiving placebo (P = .01; odds ratio [OR], 42; 95% confidence interval [CI], 2.3-760). Clinical response (reduction of ≥3 points in SCCAI) was achieved by 17 patients (65.3%) in the curcumin group vs. 3 patients (12.5%) in the placebo group (P < .001; OR, 13.2; 95% CI, 3.1-56.6). Endoscopic remission (partial Mayo score ≤1) was observed in 8 of the 22 patients evaluated in the curcumin group (38%), compared with none of 16 patients evaluated in the placebo group (P = .043; OR, 20.7; 95% CI, 1.1-393). Adverse events were rare and comparable between the 2 groups. Addition of curcumin to mesalamine therapy was superior to the combination of placebo and mesalamine in inducing clinical and endoscopic remission in patients with mild-to-moderate active UC, producing no apparent adverse effects. Curcumin may be a safe and promising agent for treatment of UC. Clinicaltrials.gov number: NCT01320436. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Successful Use of Tocilizumab in a Patient with Coexisting Rheumatoid Arthritis and Ulcerative Colitis

PubMed Central

Yalçın, Metin Devrim; Khan, Abdul; Piotrowicz, Andrzej

2016-01-01

Tocilizumab is an interleukin-6 receptor inhibitor licensed for moderate to severe rheumatoid arthritis (RA). We report a case of Tocilizumab monotherapy for severe active RA in a patient with coexisting ulcerative colitis (UC). The patient was intolerant to multiple disease-modifying drugs, so Tocilizumab monotherapy was commenced. We found clinical improvement in both RA and UC. There was no major adverse event after 2 years. Manufacturer advised caution in using Tocilizumab in patient with gastrointestinal ulceration due to an increased risk of bowel perforation. However, alternative treatments such as glucocorticoid and nonsteroidal anti-inflammatory drugs may carry a higher bowel perforation risk. The presence of gastrointestinal ulceration therefore should not constitute an absolute contraindication for Tocilizumab therapy. Future studies of registry data will inform clinician of the Tocilizumab-related risk of gastrointestinal toxicity in “real-life” settings. Contrary to previous case report, we found Tocilizumab therapy to have a positive effect on UC. Laboratory studies supported a role for interleukin-6 in the pathophysiology of UC. Further clinical trial to evaluate the therapeutic role of Tocilizumab in UC would be warranted. PMID:27818807

Physician Perspectives on Unresolved Issues in the Management of Ulcerative Colitis: The UC Horizons Project.

PubMed

Gisbert, Javier P; Barreiro-de Acosta, Manuel; Esteve, María; García-Sánchez, Valle; Gomollón, Fernando; Guardiola, Jordi; Hinojosa, Joaquin; Martín Arranz, Maria-Dolores; Minguez, Miguel; Taxonera, Carlos; Vera, Isabel

2016-03-01

There is still uncertainty about what constitutes the best therapeutic practice in ulcerative colitis (UC). The purpose of the "UC Horizons Project" was to raise a series of questions regarding the management of UC to provide responses based on the best scientific evidence available. The 11 members of the scientific committee prepared draft answers to the 10 questions from available evidence after a literature search. A total of 48 Spanish gastroenterology specialists nationwide participated in the project. The national meeting discussed the 10 issues in working groups and reached consensus regarding the recommendations by anonymous, interactive vote following the Delphi methodology. Final answers were developed, based on evidence and clinical experience of the participants. All the recommendations achieved a high level of agreement in the plenary vote, although the quality of the evidence was markedly heterogeneous. The lowest percentage of agreement corresponded to the questions with the weakest level of evidence, highlighting the necessity of conducting further studies in these areas. The recommendations focused on (1) aminosalicylates therapy (regarding dose and appropriateness of coadministration with thiopurines), (2) corticosteroid therapy (regarding dose and route of administration), (3) thiopurine treatment (regarding indications and possibility of withdrawal), (4) anti-tumor necrosis factor therapy (regarding appropriateness of combination with thiopurines, intensification, or discontinuation of treatment), and (5) colorectal cancer (regarding risk and time trends). The UC Horizons Project raised a series of eminently practical questions about the management of UC and provided responses based on the best scientific evidence available.

Relationship between physician-based assessment of disease activity, quality of life, and costs of ulcerative colitis in Poland

PubMed Central

Stawowczyk, Ewa

2018-01-01

Introduction Ulcerative colitis (UC) is an idiopathic inflammatory bowel disorder, which requires lifelong treatment. It generates substantial direct and indirect costs, and significantly affects the quality of life, especially in the active state of the disease. Aim To evaluate the direct and indirect costs of UC as well as to assess disease activity and quality of life reported by patients with UC in Polish settings. Material and methods A questionnaire, cross-sectional study among UC patients as well as physicians involved in the therapy of the patients was conducted. The Clinical Activity Index (CAI) was used to assess disease activity, and the WPAI questionnaire to assess productivity loss. The quality of life was presented as utility calculated using the EQ-5D-3L questionnaire. Indirect costs included absenteeism, presenteeism, and informal care were assessed with the Human Capital Approach and expressed in euros (€). The productivity loss among informal caregivers was valuated with the average wage in Poland. Correlations were presented using the Spearman’s coefficient, and the between-group difference was assessed with Mann-Whitney U-test. Results One hundred and forty-seven patients participated in the study, including 95 working persons. Mean cost of absenteeism and presenteeism was €1615.2 (95% CI: 669.5–2561.0) and €3684.4 (95% CI: 2367.8–5001.1), respectively, per year per patient with a disease in remission. The mean yearly cost of productivity loss due to informal care was estimated to be €256.6 (range: 0.0–532.6). The corresponding values for patients with active disease were: €8,913.3 (95% CI: 6223.3–11,603.3), €4325.1 (95% CI: 2282.4–6367.8), and €2396.1 (95% CI: 402.0–4390.3). The between-group difference in total indirect costs, cost of absenteeism, and cost of informal care was statistically significant (p < 0.05). The average weighted monthly costs of therapy with particular drugs categories (e.g. mesalazine or

Characterization of IBS-like symptoms in patients with ulcerative colitis in clinical remission.

PubMed

Jonefjäll, B; Strid, H; Ohman, L; Svedlund, J; Bergstedt, A; Simren, M

2013-09-01

Gastrointestinal symptoms compatible with Irritable Bowel Syndrome (IBS) are common in patients with inflammatory bowel disease. It has been suggested that these symptoms are a reflection of occult inflammation rather than coexisting IBS. The aim of this study was to characterize IBS-like symptoms in patients with Ulcerative Colitis (UC) in clinical remission by assessing inflammatory markers, psychological symptoms, and quality of life. Ninety-four patients with new onset of UC were followed prospectively during 3 years with yearly follow-up visits. The patients completed self-administrated questionnaires. Fecal calprotectin was used as an inflammatory biomarker. Remission was defined as a total Mayo-score ≤2 and an endoscopic subscore ≤1, with no relapse during the 3-month period prior to visit. The prevalence of patients that fulfilled Rome II criteria for IBS among UC patients in remission was 11% at visit 1, 23% at visit 2, and 17% at visit 3. When comparing UC patients in remission with and without IBS-like symptom, patients with IBS-like symptoms had more severe gastrointestinal symptoms, tendencies toward more severe psychological symptoms and reduced levels of quality of life, but the calprotectin levels did not differ between the two groups. IBS-like symptoms are common in patients with UC in clinical remission and these fluctuate over time. The symptoms are associated with poor psychological well-being and reduced quality of life, and do not seem to be a reflection of low-grade inflammatory activity. © 2013 John Wiley & Sons Ltd.

Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis: subgroup analyses from three phase 3 multinational studies.

PubMed

Motoya, Satoshi; Watanabe, Mamoru; Kim, Hyo Jong; Kim, Young Ho; Han, Dong Soo; Yuasa, Hirotoshi; Tabira, Junichi; Isogawa, Naoki; Arai, Shoko; Kawaguchi, Isao; Hibi, Toshifumi

2018-04-01

Tofacitinib is an oral, small-molecule Janus kinase inhibitor being investigated for ulcerative colitis (UC). In OCTAVE Induction 1 and 2, patients with moderately to severely active UC received placebo or tofacitinib 10 mg twice daily (BID) for 8 weeks. Clinical responders in OCTAVE Induction were re-randomized to 52 weeks' therapy with placebo, tofacitinib 5 mg BID, or tofacitinib 10 mg BID. We conducted post-hoc efficacy and safety analyses of East Asian patients in OCTAVE Induction 1 and 2 and OCTAVE Sustain. A total of 121 East Asian (Japan, Korea, and Taiwan) patients were randomized in OCTAVE Induction 1 and 2 (placebo, n=26; tofacitinib 10 mg BID, n=95), and 63 in OCTAVE Sustain (placebo, n=20; tofacitinib 5 mg BID, n=22; tofacitinib 10 mg BID, n=21). At week 8 of OCTAVE Induction 1 and 2, 18.9% of patients (18/95) achieved remission with tofacitinib 10 mg BID versus 3.8% (1/26) with placebo. In OCTAVE Sustain, the week 52 remission rates were 45.5% (10/22), 47.6% (10/21), and 15.0% (3/20) with 5 mg BID, 10 mg BID, and placebo, respectively. Adverse event rates were similar between groups in OCTAVE Induction and numerically higher with tofacitinib in OCTAVE Sustain. Serious adverse event rates were similar across groups in all studies. Infections were numerically more frequent with tofacitinib than placebo. Increases in serum lipid levels were observed with tofacitinib. In East Asian patients with UC, tofacitinib demonstrated numerically greater efficacy versus placebo as induction and maintenance therapy, with a safety profile consistent with the global study population. ClinicalTrials.gov: NCT01465763; NCT01458951; NCT01458574.

MF2KtoMF05UC, a Program To Convert MODFLOW-2000 Files to MODFLOW-2005 and UCODE_2005 Files

USGS Publications Warehouse

Harbaugh, Arlen W.

2007-01-01

The program MF2KtoMF05UC has been developed to convert MODFLOW-2000 input files for use by MODFLOW-2005 and UCODE_2005. MF2KtoMF05UC was written in the Fortran 90 computer language. This report documents the use of MF2KtoMF05UC.

Long-term outcome of patients with distal ulcerative colitis and inflammation of the appendiceal orifice.

PubMed

Naves, Juan E; Lorenzo-Zúñiga, Vicente; Marín, Laura; Mañosa, Míriam; Oller, Blanca; Moreno, Vicente; Zabana, Yamile; Boix, Jaume; Cabré, Eduard; Domènech, Eugeni

2011-12-01

Skip inflammation of the appendiceal orifice has been described in distal UC (UC-IAO) but long-term clinical outcomes are poorly established. Our aim was to evaluate the long-term clinical outcomes of UC-IAO as compared to classic distal UC. Patients with UC-IAO were identified from the local IBD database. Disease outcome and therapeutic requirements during follow-up were accurately collected, and compared with a control group of patients with distal UC without peri-appendiceal involvement matched by disease extent (proctitis/distal), smoking habit, and date and age at diagnosis. Fourteen UC patients were found to have UC-IAO, most of them with initial extent of UC limited to the rectum. All patients were initially managed with mesalazine administered orally (28.5%), topically (28.5%), or in combination (43%). After a median follow-up of 78 months (interquartile range--IQR 45-123) most UC-IAO patients were successfully managed with oral and/or topical aminosalicylates. Only one of them developed proximal disease progression. As compared to controls, no differences in clinical outcomes or therapeutic requirements were found. Patients with UC-IAO tend to present a mild course, with a low probability to develop proximal progression of disease extent or to require immunosuppressive therapy or colectomy.

C. Judson King of UC Berkeley

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

Prausnitz, John

2005-06-01

In the middle of the UC Berkeley campus, next to the Main Library, South Hall is the last surviving building from the original campus, founded about 135 years ago. A tiny tree-shaded appendix to this venerated classical building houses Berkeley's Center for Studies in Higher Education, directed by C. Judson King, former Provost and Senior Vice President--Academic Affairs of the ten-campus University of California and long-time Professor of Chemical Engineering at Berkeley. Jud came to Berkeley in 1963 as assistant professor of chemical engineering, following receipt of a doctor's degree from MIT and a subsequent short appointment as director ofmore » the MIT chemical engineering practice school station at what was then Esso (now Exxon) in New Jersey. His undergraduate degree is from Yale. Starting with his MIT doctoral dissertation on gas absorption, Jud has devoted much of his professional career to separation processes. His teaching and research activities have been primarily concerned with separation of mixtures with emphasis on liquid-liquid extraction and drying. As a consultant to Procter and Gamble, he contributed to the technology of making instant coffee. His life-long activities in hiking and camping stimulated Jud's interest in the manufacture of freeze-dried foods (e.g. turkey meat) to minimize the weight of his hiking back-pack. Jud is internationally known not only for his many research publications but even more, for his acclaimed textbook ''Separation Processses'' (McGraw-Hill, second edition 1980) that is used in standard chemical engineering courses in the US and abroad.« less

Ultrasound discloses entheseal involvement in inactive and low active inflammatory bowel disease without clinical signs and symptoms of spondyloarthropathy.

PubMed

Bandinelli, Francesca; Milla, Monica; Genise, Stefania; Giovannini, Leonardo; Bagnoli, Siro; Candelieri, Antonio; Collaku, Ledio; Biagini, Silvia; Cerinic, Marco Matucci

2011-07-01

To investigate the presence of lower limb entheseal abnormalities in IBD patients without clinical signs and symptoms of SpA and their correlation with IBD clinical variables. A total of 81 IBD patients [55 Crohn's disease (CD) and 26 ulcerative colitis (UC), 43 females and 38 males, mean age 41.3 (12.4) years, BMI 24 (2)] with low active (12) and inactive (67) disease were consecutively studied with US (LOGIQ5 General Electric 10-MHz linear array transducer) of lower limb entheses and compared with 40 healthy controls matched for sex, age and BMI. Quadriceps, patellar, Achilleon and plantar fascia entheses were scored according to the 0-36 Glasgow Ultrasound Enthesitis Scoring System (GUESS) and power Doppler (PD). Correlations of GUESS and PD with IBD features [duration, type (CD/UC) and activity (disease activity index for CD/Truelove score for UC)] were investigated. The intra- and inter-reader agreements for US were estimated in all images detected in patients and controls. Of the 81 patients, 71 (92.6%) presented almost one tendon alteration with mean GUESS 5.1 (3.5): 81.5% thickness (higher than controls P < 0.05), 67.9% enthesophytosis, 27.1% bursitis and 16.1% erosions. PD was positive in 13/81 (16%) patients. In controls, US showed only enthesophytes (5%) and no PD. GUESS and PD were independent of duration, activity or type (CD/UC) of IBD. The intra- and inter-reader agreements were high (>0.9 intra-class correlation variability). US entheseal abnormalities are present in IBD patients without clinical signs and symptoms of SpA. US enthesopathy is independent of activity, duration and type of gut disease.

UNC-45/CRO1/She4p (UCS) Protein Forms Elongated Dimer and Joins Two Myosin Heads Near Their Actin Binding Region

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

H Shi; G Blobel

2011-12-31

UNC-45/CRO1/She4p (UCS) proteins have variously been proposed to affect the folding, stability, and ATPase activity of myosins. They are the only proteins known to interact directly with the motor domain. To gain more insight into UCS function, we determined the atomic structure of the yeast UCS protein, She4p, at 2.9 {angstrom} resolution. We found that 16 helical repeats are organized into an L-shaped superhelix with an amphipathic N-terminal helix dangling off the short arm of the L-shaped molecule. In the crystal, She4p forms a 193-{angstrom}-long, zigzag-shaped dimer through three distinct and evolutionary conserved interfaces. We have identified She4p's C-terminal regionmore » as a ligand for a 27-residue-long epitope on the myosin motor domain. Remarkably, this region consists of two adjacent, but distinct, binding epitopes localized at the nucleotide-responsive cleft between the nucleotide- and actin-filament-binding sites. One epitope is situated inside the cleft, the other outside the cleft. After ATP hydrolysis and Pi ejection, the cleft narrows at its base from 20 to 12 {angstrom} thereby occluding the inside the cleft epitope, while leaving the adjacent, outside the cleft binding epitope accessible to UCS binding. Hence, one cycle of higher and lower binding affinity would accompany one ATP hydrolysis cycle and a single step in the walk on an actin filament rope. We propose that a UCS dimer links two myosins at their motor domains and thereby functions as one of the determinants for step size of myosin on actin filaments.« less

Environmental Profiles of Paper vs. Electronic UC-CEAS Annual Reports

EPA Science Inventory

In 2010, the University of Cincinnati College of Engineering and Applied Sciences (UC-CEAS) created a new electronic format for the Annual Report that could be distributed through the college’s website to replace the prior print version. In order to determine the environmental co...

Healthcare Utilisation and Drug Treatment in a Large Cohort of Patients with Inflammatory Bowel Disease

PubMed Central

Wettermark, Björn; Löfberg, Robert; Eriksson, Irene; Sundström, Johan; Lördal, Mikael

2016-01-01

Background and Aims: Crohn’s disease [CD] and ulcerative colitis [UC] are chronic diseases associated with a substantial utilisation of healthcare resources. We aimed to estimate the prevalence of inflammatory bowel disease [IBD], CD, and UC and to describe and compare healthcare utilisation and drug treatment in CD and UC patients. Methods: This was a cross-sectional study of all patients with a recorded IBD diagnosis in Stockholm County, Sweden. Data on outpatient visits, hospitalisations, surgeries, and drug treatment during 2013 were analysed. Results: A total of 13 916 patients with IBD were identified, corresponding to an overall IBD prevalence of 0.65% [CD 0.27%, UC 0.35%, inflammatory bowel disease unclassified 0.04%]; 49% of all IBD patients were treated with IBD-related drugs. Only 3.6% of the patients received high-dose corticosteroids, whereas 32.4% were treated with aminosalicylates [CD 21.2%, UC 41.0%, p < 0.0001]. More CD patients were treated with biologicals compared with UC patients [CD 9.6%, UC 2.9%, p < 0.0001] and surgery was significantly more common among CD patients [CD 3.0%, UC 0.8%, p < 0.0001]. Conclusions: This study indicates that patients with CD are the group with the highest medical needs. Patients with CD utilised significantly more healthcare resources [including outpatient visits, hospitalisations, and surgeries] than UC patients. Twice as many CD patients received immunomodulators compared with UC patients and CD patients were treated with biologicals three times more often. These results highlight that CD remains a challenge and further efforts are needed to improve care in these patients. PMID:26733406

Serial semi-quantitative measurement of fecal calprotectin in patients with ulcerative colitis in remission.

PubMed

Garcia-Planella, Esther; Mañosa, Míriam; Chaparro, María; Beltrán, Belén; Barreiro-de-Acosta, Manuel; Gordillo, Jordi; Ricart, Elena; Bermejo, Fernando; García-Sánchez, Valle; Piqueras, Marta; Llaó, Jordina; Gisbert, Javier P; Cabré, Eduard; Domènech, Eugeni

2018-02-01

Fecal calprotectin (FC) correlates with clinical and endoscopic activity in ulcerative colitis (UC), and it is a good predictor of relapse. However, its use in clinical practice is constrained by the need for the patient to deliver stool samples, and for their handling and processing in the laboratory. The availability of hand held devices might spread the use of FC in clinical practice. To evaluate the usefulness of a rapid semi-quantitative test of FC in predicting relapse in patients with UC in remission. Prospective, multicenter study that included UC patients in clinical remission for ≥6 months on maintenance treatment with mesalamine. Patients were evaluated clinically and semi-quantitative FC was measured using a monoclonal immunochromatography rapid test at baseline and every three months until relapse or 12 months of follow-up. One hundred and ninety-one patients had at least one determination of FC. At the end of follow-up, 33 patients (17%) experienced clinical relapse. Endoscopic activity at baseline (p = .043) and having had at least one FC > 60 μg/g during the study period (p = .03) were associated with a higher risk of relapse during follow-up. We obtained a total of 636 semi-quantitative FC determinations matched with a three-month follow-up clinical assessment. Having undetectable FC was inversely associated with early relapse (within three months), with a negative predictive value of 98.6% and a sensitivity of 93.9%. Serial, rapid semi-quantitative measurement of FC may be a useful, easy and cheap monitoring tool for patients with UC in remission.

Longitudinal Analyses of Gut Mucosal Microbiotas in Ulcerative Colitis in Relation to Patient Age and Disease Severity and Duration

PubMed Central

Fite, Alemu; Furrie, Elizabeth; Bahrami, Bahram; Cummings, John H.; Steinke, Douglas T.; Macfarlane, George T.

2013-01-01

Bacteria belonging to the normal colonic microbiota are associated with the etiology of ulcerative colitis (UC). Although several mucosal species have been implicated in the disease process, the organisms and mechanisms involved are unknown. The aim of this investigation was to characterize mucosal biofilm communities over time and to determine the relationship of these bacteria to patient age and disease severity and duration. Multiple rectal biopsy specimens were taken from 33 patients with active UC over a period of 1 year. Real-time PCR was used to quantify mucosal bacteria in UC patients compared to 18 noninflammatory bowel disease controls, and the relationship between indicators of disease severity and bacterial colonization was evaluated by linear regression analysis. Significant differences were detected in bacterial populations on the UC mucosa and in the control group, which varied over the study period. High clinical activity indices (CAI) and sigmoidoscopy scores (SS) were associated with enterobacteria, desulfovibrios, type E Clostridium perfringens, and Enterococcus faecalis, whereas the reverse was true for Clostridium butyricum, Ruminococcus albus, and Eubacterium rectale. Lactobacillus and bifidobacterium numbers were linked with low CAI. Only E. rectale and Clostridium clostridioforme had a high age dependence. These findings demonstrated that longitudinal variations in mucosal bacterial populations occur in UC and that bacterial community structure is related to disease severity. PMID:23269735

Urinary potassium is a potential biomarker of disease activity in Ulcerative colitis and displays in vitro immunotolerant role.

PubMed

Goyal, Sandeep; Rampal, Ritika; Kedia, Saurabh; Mahajan, Sandeep; Bopanna, Sawan; Yadav, Devesh P; Jain, Saransh; Singh, Amit Kumar; Wari, Md Nahidul; Makharia, Govind; Awasthi, Amit; Ahuja, Vineet

2017-12-22

We evaluated the in-vitro effect of potassium on CD4 + T cells and the role of urinary potassium as a potential biomarker of disease activity in patients with ulcerative colitis (UC). This prospective observational cohort study included healthy controls (n = 18) and UC patients [n = 30, median age: 40 (IQR: 28-46) years, 17 males)] with active disease(assessed by Mayo score) from September 2015-May 2016. Twenty-four hours urinary potassium along with fecal calprotectin (FCP) were estimated in UC patients (at baseline and follow-up after 3-6 months) and controls. In healthy volunteers, we also assessed the effect of potassium on CD4 + T cells differentiated in the presence of Th17 polarizing condition. UC patients had significantly higher FCP (368.2 ± 443.04 vs 12.44 ± 27.51, p < 0.001) and significantly lower urinary potassium (26.6 ± 16.9 vs 46.89 ± 35.91, p = 0.01) levels than controls. At follow-up, a significant increase in urinary potassium among patients who had clinical response [n = 22, 21.4 (14.4-39.7) to 36.5 (20.5-61.6), p = 0.04] and remission [n = 12, 18.7 (9.1-34.3) to 36.5 (23.4-70.5), p = 0.05] was accompanied with a parallel decline in FCP. On in-vitro analysis, potassium under Th17 polarizing conditions significantly inhibited IL-17 and interferon-[Formula: see text] expression while favoring the induction of FoxP3 + T cells. Therefore, urinary potassium levels are inversely associated with disease activity in UC with in-vitro data supporting an immune-tolerant role of potassium.

Intestinal interleukin-13 in pediatric inflammatory bowel disease patients.

PubMed

Kadivar, Khadijeh; Ruchelli, Eduardo D; Markowitz, Jonathan E; Defelice, Magee L; Strogatz, Melissa L; Kanzaria, Mitul M; Reddy, Krishna P; Baldassano, Robert N; von Allmen, Daniel; Brown, Kurt A

2004-09-01

Interleukin-13 (IL-13) is a multifunctional cytokine whose net principle action is to diminish inflammatory responses. Dysregulation of IL-13 production has been proposed to contribute to intestinal inflammation in inflammatory bowel disease (IBD) patients. Previous studies implicate IL-13 in IBD pathogenesis; however, they fail to accurately reflect in vivo intestinal IL-13 production. We evaluate IL-13, IL-6, and IL-1beta elaborations from colonic organ cultures of pediatric IBD patients Endoscopic lamina propria biopsies or surgical specimens from pediatric patients with IBD were organ cultured and supernatants evaluated by enzyme-linked immunosorbent assay for IL-1beta, IL-6, and IL-13. IL-13 concentrations were significantly reduced in ulcerative colitis (UC) patients when compared with normal controls (P = 0.002) and Crohn disease (CD) patients (P = 0.001). End-stage UC patients at colectomy had lower intestinal IL-13 production than all other UC patients (P = 0.002). No significant correlation was found between IL-13 concentration and histologic disease severity (P = 0.134). Diminished intestinal IL-13 production is present in UC patients and wanes further with clinical disease progression. These findings suggest that UC patients may be differentiated from CD patients by intestinal IL-13 quantitation, and UC patients may benefit from IL-13 enhancing therapies. Copyright 2004 Lippincott Williams & Wilkins

Clinical course of ulcerative colitis patients who develop acute pancreatitis.

PubMed

Kim, Jong Wook; Hwang, Sung Wook; Park, Sang Hyoung; Song, Tae Jun; Kim, Myung-Hwan; Lee, Ho-Su; Ye, Byong Duk; Yang, Dong-Hoon; Kim, Kyung-Jo; Byeon, Jeong-Sik; Myung, Seung-Jae; Yang, Suk-Kyun

2017-05-21

To investigate the clinical course of ulcerative colitis (UC) patients who develop acute pancreatitis. We analyzed 3307 UC patients from the inflammatory bowel disease registry at Asan Medical Center from June 1989 to May 2015. The clinical course of UC patients who developed acute pancreatitis was compared with that of non-pancreatitis UC patients. Among 51 patients who developed acute pancreatitis, 13 (0.40%) had autoimmune, 10 (0.30%) had aminosalicylate-induced, and 13 (1.73%) had thiopurine-induced pancreatitis. All 13 patients with autoimmune pancreatitis (AIP) had type 2 AIP. Two (15.4%) patients had pre-existing AIP, and three (23.1%) patients developed AIP and UC simultaneously. Compared to non-pancreatitis patients, AIP patients had UC diagnosed at a significantly younger age (median, 22.9 years vs 36.4 years; P = 0.001). AIP and aminosalicylate-induced pancreatitis patients had more extensive UC compared to non-pancreatitis patients. All patients with pancreatitis recovered uneventfully, and there were no recurrences. Biologics were used more frequently in aminosalicylate- and thiopurine-induced pancreatitis patients compared to non-pancreatitis patients [adjusted OR (95%CI), 5.16 (1.42-18.67) and 6.90 (1.83-25.98), respectively]. Biologic utilization rate was similar among AIP and non-pancreatitis patients [OR (95%CI), 0.84 (0.11-6.66)]. Colectomy rates for autoimmune, aminosalicylate-induced, and thiopurine-induced pancreatitis, and for non-pancreatitis patients were 15.4% (2/13), 20% (2/10), 15.4% (2/13), and 7.3% (239/3256), respectively; the rates were not significantly different after adjusting for baseline disease extent. Pancreatitis patients show a non-significant increase in colectomy, after adjusting for baseline disease extent.

Mucosal and invading bacteria in patients with inflammatory bowel disease compared with controls.

PubMed

Kleessen, B; Kroesen, A J; Buhr, H J; Blaut, M

2002-09-01

Endogenous intestinal bacteria and/or specific bacterial pathogens are suspected of being involved in the pathogenesis of inflammatory bowel diseases (IBD). The aim of this study was to investigate IBD tissues for different bacterial population groups harbouring the mucosal surface and/or invading the mucosa. Tissue sections from surgical resections from the terminal ileum and/or the colon from 24 IBD patients (12 active ulcerative colitis (UC), 12 active Crohn disease (CD)) and 14 non-IBD controls were studied by fluorescent in situ hybridization on a quantifiable basis. More bacteria were detected on the mucosal surface of IBD patients than on those of non-IBD controls (P < 0.05). Bacterial invasion of the mucosa was evident in 83.3% of colonic specimens from the UC patients, in 55.6% of the ileal and in 25% of the colonic specimens from the CD patients, but no bacteria were detected in the tissues of the controls. Colonic UC specimens were colonized by a variety of organisms, such as bacteria belonging to the gamma subdivision of Proteobacteria, the Enterobacteriaceae, the Bacteroides/Prevotella cluster, the Clostridium histolyticum/Clostridium lituseburense group, the Clostridium coccoides/Eubacterium rectale group, high G + C Gram-positive bacteria, or sulphate-reducing bacteria, while CD samples harboured mainly bacteria belonging to the former three groups. Pathogenic events in CD and UC may be associated with different alterations in the mucosal flora of the ileum and colon.

Exercise capacity in pediatric patients with inflammatory bowel disease.

PubMed

Ploeger, Hilde E; Takken, Tim; Wilk, Boguslaw; Issenman, Robert M; Sears, Ryan; Suri, Soni; Timmons, Brian W

2011-05-01

To examine exercise capacity in youth with Crohn's disease (CD) and ulcerative colitis (UC). Eleven males and eight females with CD and six males and four females with UC participated. Patients performed standard exercise tests to assess peak power (PP) and mean power (MP) and peak aerobic mechanical power (W(peak)) and peak oxygen uptake (VO(2peak)). Fitness variables were compared with reference data and also correlated with relevant clinical outcomes. Pediatric patients with inflammatory bowel disease had lower PP (∼90% of predicted), MP (∼88% of predicted), W(peak) (∼91% of predicted), and VO(2peak) (∼75% of predicted) compared with reference values. When patients with CD or UC were compared separately to reference values, W(peak) was significantly lower only in the CD group. No statistically significant correlations were found between any exercise variables and disease duration (r = 0.01 to 0.14, P = .47 to .95) or disease activity (r = -0.19 to -0.31, P = .11 to .38), measured by pediatric CD activity index or pediatric ulcerative colitis activity index. After controlling for chronological age, recent hemoglobin levels were significantly correlated with PP (r = 0.45, P = .049), MP (r = 0.63, P = .003), VO(2peak) (r = 0.62, P = .004), and W(peak) (r = 0.70, P = .001). Pediatric patients with inflammatory bowel disease exhibit impaired aerobic and anaerobic exercise capacity compared with reference values. Copyright © 2011 Mosby, Inc. All rights reserved.

Cannabis use amongst patients with inflammatory bowel disease.

PubMed

Lal, Simon; Prasad, Neeraj; Ryan, Manijeh; Tangri, Sabrena; Silverberg, Mark S; Gordon, Allan; Steinhart, Hillary

2011-10-01

Experimental evidence suggests the endogenous cannabinoid system may protect against colonic inflammation, leading to the possibility that activation of this system may have a therapeutic role in inflammatory bowel disease (IBD). Medicinal use of cannabis for chronic pain and other symptoms has been reported in a number of medical conditions. We aimed to evaluate cannabis use in patients with IBD. One hundred patients with ulcerative colitis (UC) and 191 patients with Crohn's disease (CD) attending a tertiary-care outpatient clinic completed a questionnaire regarding current and previous cannabis use, socioeconomic factors, disease history and medication use, including complimentary alternative medicines. Quality of life was assessed using the short-inflammatory bowel disease questionnaire. A comparable proportion of UC and CD patients reported lifetime [48/95 (51%) UC vs. 91/189 (48%) CD] or current [11/95 (12%) UC vs. 30/189 (16%) CD] cannabis use. Of lifetime users, 14/43 (33%) UC and 40/80 (50%) CD patients have used it to relieve IBD-related symptoms, including abdominal pain, diarrhoea and reduced appetite. Patients were more likely to use cannabis for symptom relief if they had a history of abdominal surgery [29/48 (60%) vs. 24/74 (32%); P=0.002], chronic analgesic use [29/41 (71%) vs. 25/81 (31%); P<0.001], complimentary alternative medicine use [36/66 (55%) vs. 18/56 (32%); P=0.01] and a lower short inflammatory bowel disease questionnaire score (45.1±2.1 vs. 50.3±1.5; P=0.03). Patients who had used cannabis [60/139 (43%)] were more likely than nonusers [13/133 (10%); P<0.001 vs. users] to express an interest in participating in a hypothetical therapeutic trial of cannabis for IBD. Cannabis use is common amongst patients with IBD for symptom relief, particularly amongst those with a history of abdominal surgery, chronic abdominal pain and/or a low quality of life index. The therapeutic benefits of cannabinoid derivatives in IBD may warrant further

Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis.

PubMed

Costello, S P; Soo, W; Bryant, R V; Jairath, V; Hart, A L; Andrews, J M

2017-08-01

Faecal microbiota transplantation (FMT) is emerging as a novel therapy for ulcerative colitis (UC). Interpretation of efficacy of FMT for UC is complicated by differences among studies in blinding, FMT administration procedures, intensity of therapy and donor stool processing methods. To determine whether FMT is effective and safe for the induction of remission in active UC. Medline (Ovid), Embase and the Cochrane Library were searched from inception through February 2017. Original studies reporting remission rates following FMT for active UC were included. All study designs were included in the systematic review and a meta-analysis performed including only randomised controlled trials (RCTs). There were 14 cohort studies and four RCTs that used markedly different protocols. In the meta-analysis of RCTs, clinical remission was achieved in 39 of 140 (28%) patients in the donor FMT groups compared with 13 of 137 (9%) patients in the placebo groups; odds ratio 3.67 (95% CI: 1.82-7.39, P<.01). Clinical response was achieved in 69 of 140 (49%) donor FMT patients compared to 38 of 137 (28%) placebo patients; odds ratio 2.48 (95% CI: 1.18-5.21, P=.02). In cohort studies, 39 of 168 (24%; 95% CI: 11%-40%) achieved clinical remission. Despite variation in processes, FMT appears to be effective for induction of remission in UC, with no major short-term safety signals. Further studies are needed to better define dose frequency and preparation methods, and to explore its feasibility, efficacy and safety as a maintenance agent. © 2017 John Wiley & Sons Ltd.

Fecal immunochemical test for predicting mucosal healing in ulcerative colitis patients: A systematic review and meta-analysis.

PubMed

Dai, Cong; Jiang, Min; Sun, Ming-Jun; Cao, Qin

2018-05-01

Fecal immunochemical test (FIT) is a promising marker for assessment of inflammatory bowel disease activity. However, the utility of FIT for predicting mucosal healing (MH) of ulcerative colitis (UC) patients has yet to be clearly demonstrated. The objective of our study was to perform a diagnostic test accuracy test meta-analysis evaluating the diagnostic accuracy of FIT in predicting MH of UC patients. We systematically searched the databases from inception to November 2017 that evaluated MH in UC. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. The extracted data were pooled using a summary receiver operating characteristic curve model. Random-effects model was used to summarize the diagnostic odds ratio, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. Six studies comprising 625 UC patients were included in the meta-analysis. The pooled sensitivity and specificity values for predicting MH in UC were 0.77 (95% confidence interval [CI], 0.72-0.81) and 0.81 (95% CI, 0.76-0.85), respectively. The FIT level had a high rule-in value (positive likelihood ratio, 3.79; 95% CI, 2.85-5.03) and a moderate rule-out value (negative likelihood ratio, 0.26; 95% CI, 0.16-0.43) for predicting MH in UC. The results of the receiver operating characteristic curve analysis (area under the curve, 0.88; standard error of the mean, 0.02) and diagnostic odds ratio (18.08; 95% CI, 9.57-34.13) also revealed improved discrimination for identifying MH in UC with FIT concentration. Our meta-analysis has found that FIT is a simple, reliable non-invasive marker for predicting MH in UC patients. © 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Efficacy of vedolizumab as induction therapy in refractory IBD patients: Amulticenter cohort

PubMed Central

Shelton, Edward; Allegretti, Jessica R.; Stevens, Betsy; Lucci, Matthew; Khalili, Hamed; Nguyen, Deanna D.; Sauk, Jenny; Giallourakis, Cosmas; Garber, John; Hamilton, Matthew J; Tomczak, Michal; Makrauer, Fredrick; Burakoff, Robert B; Levine, Jonathan; de Silva, Punyaganie; Friedman, Sonia; Ananthakrishnan, Ashwin; Korzenik, Joshua R.; Yajnik, Vijay

2015-01-01

Background Vedolizumab (VDZ) demonstrated efficacy in Crohn's disease (CD) and ulcerative colitis (UC) in the GEMINI trials. Our aim was to evaluate the efficacy of VDZ at week 14 in inflammatory bowel disease (IBD) in a multicenter cohort of patients. Methods Patients at Massachusetts General Hospital and Brigham and Women's Hospital were considered for inclusion. VDZ (300mg) was administered at weeks 0, 2, 6 and 14. Efficacy was assessed using the Harvey Bradshaw index (HBI) for CD, the simple clinical colitis activity index (SCCAI) for UC and physician assessment, along with C-reactive protein (CRP) and decrease of corticosteroid therapy. Clinical response was defined as decrease in HBI ≥ 3 and SCCAI ≥ 3 and remission as HBI ≤ 4, SCCAI ≤ 2 and physician assessment of response and remission. Results Our study included 172 patients (107 CD, 59 UC, 6 IBD-U, male 48.3%, mean age 40 years and disease duration 14 years). Fourteen patients had an ostomy and 9 an ileoanal pouch and only 35.5% fulfilled eligibility for the GEMINI trials. Previous treatment failures with ≥ 2 anti-TNFs occurred in 70.9%, one-third were on an immunomodulator and 46% systemic steroids at baseline. In CD, 48.9% and 23.9% and in UC, 53.9% and 29.3% had clinical response and clinical remission at week 14. Adverse events occurred in 10.5%. Conclusions VDZ is safe and well tolerated in refractory IBD patients in a clinical practice with efficacy in UC and CD with responses similar to what was seen in clinical trials. PMID:26288002

Development and Validation of an Inflammatory Bowel Diseases Monitoring Index for Use With Mobile Health Technologies.

PubMed

Van Deen, Welmoed K; van der Meulen-de Jong, Andrea E; Parekh, Nimisha K; Kane, Ellen; Zand, Aria; DiNicola, Courtney A; Hall, Laurin; Inserra, Elizabeth K; Choi, Jennifer M; Ha, Christina Y; Esrailian, Eric; van Oijen, Martijn G H; Hommes, Daniel W

2016-12-01

Mobile health technologies are advancing rapidly as smartphone use increases. Patients with inflammatory bowel disease (IBD) might be managed remotely through smartphone applications, but no tools are yet available. We tested the ability of an IBD monitoring tool, which can be used with mobile technologies, to assess disease activity in patients with Crohn's disease (CD) or ulcerative colitis (UC). We performed a prospective observational study to develop and validate a mobile health index for CD and UC, which monitors IBD disease activity using patient-reported outcomes. We collected data from disease-specific questionnaires completed by 110 patients with CD and 109 with UC who visited the University of California, Los Angeles, Center for IBD from May 2013 through January 2014. Patient-reported outcomes were compared with clinical disease activity index scores to identify factors associated with disease activity. Index scores were validated in 301 patients with CD and 265 with UC who visited 3 tertiary IBD referral centers (in California or Europe) from April 2014 through March 2015. We assessed activity of CD based on liquid stool frequency, abdominal pain, patient well-being, and patient-assessed disease control, and activity of UC based on stool frequency, abdominal pain, rectal bleeding, and patient-assessed disease control. The indices identified clinical disease activity with area under the receiver operating characteristic curve values of 0.90 in patients with CD and 0.91 in patients with UC. They identified endoscopic activity with area under the receiver operating characteristic values of 0.63 in patients with CD and 0.82 in patients with UC. Both scoring systems responded to changes in disease activity (P < .003). The intraclass correlation coefficient for test-retest reliability was 0.94 for CD and for UC. We developed and validated a scoring system to monitor disease activity in patients with CD and UC that can be used with mobile technologies. The

Characterization of Intestinal Microbiota in Ulcerative Colitis Patients with and without Primary Sclerosing Cholangitis.

PubMed

Kevans, D; Tyler, A D; Holm, K; Jørgensen, K K; Vatn, M H; Karlsen, T H; Kaplan, G G; Eksteen, B; Gevers, D; Hov, J R; Silverberg, M S

2016-03-01

There is an unexplained association between ulcerative colitis [UC] and primary sclerosing cholangitis [PSC], with the intestinal microbiota implicated as an important factor. The study aim was to compare the structure of the intestinal microbiota of patients with UC with and without PSC. UC patients with PSC [PSC-UC] and without PSC [UC] were identified from biobanks at Oslo University Hospital, Foothills Hospital Calgary and Mount Sinai Hospital Toronto. Microbial DNA was extracted from colonic tissue and sequencing performed of the V4 region of the 16S rRNA gene on Illumina MiSeq. Sequences were assigned to operational taxonomic units [OTUs] using Quantitative Insights Into Microbial Ecology [QIIME]. Microbial alpha diversity, beta diversity, and relative abundance were compared between PSC-UC and UC phenotypes. In all, 31 PSC-UC patients and 56 UC patients were included. Principal coordinate analysis [PCoA] demonstrated that city of sample collection was the strongest determinant of taxonomic profile. In the Oslo cohort, Chao 1 index was modestly decreased in PSC-UC compared with UC [p = 0.04] but did not differ significantly in the Calgary cohort. No clustering by PSC phenotype was observed using beta diversity measures. For multiple microbial genera there were nominally significant differences between UC and PSC-UC, but results were not robust to false-discovery rate correction. No strong PSC-specific microbial associations in UC patients consistent across different cohorts were identified. Recruitment centre had a strong effect on microbial composition. Future studies should include larger cohorts to increase power and the ability to control for confounding factors. 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.

Treatment of Ischemia-Reperfusion Injury of the Skin Flap Using Human Umbilical Cord Mesenchymal Stem Cells (hUC-MSCs) Transfected with “F-5” Gene

PubMed Central

Leng, Xiangfeng; Fan, Yongle; Wang, Yating; Sun, Jian; Cai, Xia; Hu, Chunnan; Ding, Xiaoying; Hu, Xiaoying; Chen, Zhenyu

2017-01-01

Background Recent studies have shown that skin flap transplantation technique plays an important role in surgical procedures. However, there are many problems in the process of skin flap transplantation surgeries, especially ischemia-reperfusion injury, which directly affects the survival rate of the skin flap and patient prognosis after surgeries. Material/Methods In this study, we used a new method of the “stem cells-gene” combination therapy. The “F-5” gene fragment of heat shock protein 90-α (Hsp90-α) was transfected into human umbilical cord mesenchymal stem cells (hUC-MSCs) by genetic engineering technique. Results The synergistic effects of “F-5” gene and hUC-MSCs in the treatment of ischemia-reperfusion injury of the skin flap were confirmed by histochemical and immunohistochemical methods. Conclusions This study showed that the hUC-MSCs transfected with “F-5” gene can effectively improve the repair of ischemia-reperfusion injury. PMID:28586321

Association of Clinical Features with Human Leukocyte Antigen in Japanese Patients with Ulcerative Colitis.

PubMed

Iwamoto, Taku; Yashima, Kazuo; Morio, Keiko; Ueda, Naoki; Ikebuchi, Yuichiro; Kawaguchi, Koichiro; Harada, Kenichi; Isomoto, Hajime

2018-03-01

The human leukocyte antigen (HLA) region has been found to be involved in the pathogenesis of inflammatory bowel disease (IBD), which is classified into ulcerative colitis (UC) and Crohn's disease (CD), by genome-wide association studies. The aim of this study was to confirm whether HLA-alleles confer susceptibility to UC and to determine whether HLA-allel1es are associated with the clinical phenotypes in Japanese patients with UC. In this study, HLA typing was performed by PCR-sequence-specific oligonucleotides (PCR-SSO) to confirm the correlation between UC and HLA alleles (for HLA-A, B, DRB1) in 45 Japanese UC patients. In addition, whether the HLA alleles are related to patient and clinical background characteristics was examined. Overall, 62.2%, and 66.7% of the 45 UC patients had HLA-B*52 and HLA-DRB1*15, respectively. These allele frequencies were significantly higher than in previously reported Japanese control persons ( P < 0.0001). The frequencies of extraintestinal manifestations [odds ratio (OR) = 0.12, P = 0.039] and a history of colectomy (OR = 0.18, P = 0.046) were lower in HLA-B*52-positive UC patients than in HLA-B*52 negative UC patients. The white blood cell (WBC) count was significantly higher in HLA-DRB1*15-positive patients (9430 ± 4592/μL) than in HLA-DRB1*15-negative patients (6729 ± 2160/μL). Thus, HLA-B*52 and DRB1*15 appear to be associated with disease features and severity in Japanese UC patients. These results indicate that HLA-B*52 and DRB1*15 are not only associated with overall UC susceptibility, but also with the clinical phenotypes in Japanese patients.

Pharmacological intervention based on fecal calprotectin levels in patients with ulcerative colitis at high risk of a relapse: A prospective, randomized, controlled study

PubMed Central

Öhman, Lena; Stotzer, Per-Ove; Isaksson, Stefan; Überbacher, Otto; Ung, Kjell-Arne; Strid, Hans

2015-01-01

Background Targeted therapy, using biomarkers to assess disease activity in ulcerative colitis (UC), has been proposed. Objective The objective of this study was to evaluate whether pharmacological intervention guided by fecal calprotectin (FC) prolongs remission in patients with UC. Methods A total of 91 adults with UC in remission were randomized to an intervention group or a control group. Analysis of FC was performed monthly, during 18 months. A FC value of 300 µg/g was set as the cut-off for intervention, which was a dose escalation of the oral 5-aminosalicylate (5-ASA) agent. The primary study end-point was the number of patients to have relapsed by month 18. Results There were relapses in 18 (35.3%) and 20 (50.0%) patients in the intervention and the control groups, respectively (p = 0.23); and 28 (54.9%) patients in the intervention group and 28 (70.0%) patients in the control group had a FC > 300 µg/g, of which 8 (28.6%) and 16 (57.1%) relapsed, respectively (p < 0.05). Conclusion Active intervention significantly reduced relapse rates, although no significant difference was reached between the groups overall. Thus, FC-levels might be used to identify patients with UC at risk for a flare, and a dose escalation of their 5-ASA agent is a therapeutic option for these patients. PMID:25653861

Clinical course of ulcerative colitis patients who develop acute pancreatitis

PubMed Central

Kim, Jong Wook; Hwang, Sung Wook; Park, Sang Hyoung; Song, Tae Jun; Kim, Myung-Hwan; Lee, Ho-Su; Ye, Byong Duk; Yang, Dong-Hoon; Kim, Kyung-Jo; Byeon, Jeong-Sik; Myung, Seung-Jae; Yang, Suk-Kyun

2017-01-01

AIM To investigate the clinical course of ulcerative colitis (UC) patients who develop acute pancreatitis. METHODS We analyzed 3307 UC patients from the inflammatory bowel disease registry at Asan Medical Center from June 1989 to May 2015. The clinical course of UC patients who developed acute pancreatitis was compared with that of non-pancreatitis UC patients. RESULTS Among 51 patients who developed acute pancreatitis, 13 (0.40%) had autoimmune, 10 (0.30%) had aminosalicylate-induced, and 13 (1.73%) had thiopurine-induced pancreatitis. All 13 patients with autoimmune pancreatitis (AIP) had type 2 AIP. Two (15.4%) patients had pre-existing AIP, and three (23.1%) patients developed AIP and UC simultaneously. Compared to non-pancreatitis patients, AIP patients had UC diagnosed at a significantly younger age (median, 22.9 years vs 36.4 years; P = 0.001). AIP and aminosalicylate-induced pancreatitis patients had more extensive UC compared to non-pancreatitis patients. All patients with pancreatitis recovered uneventfully, and there were no recurrences. Biologics were used more frequently in aminosalicylate- and thiopurine-induced pancreatitis patients compared to non-pancreatitis patients [adjusted OR (95%CI), 5.16 (1.42-18.67) and 6.90 (1.83-25.98), respectively]. Biologic utilization rate was similar among AIP and non-pancreatitis patients [OR (95%CI), 0.84 (0.11-6.66)]. Colectomy rates for autoimmune, aminosalicylate-induced, and thiopurine-induced pancreatitis, and for non-pancreatitis patients were 15.4% (2/13), 20% (2/10), 15.4% (2/13), and 7.3% (239/3256), respectively; the rates were not significantly different after adjusting for baseline disease extent. CONCLUSION Pancreatitis patients show a non-significant increase in colectomy, after adjusting for baseline disease extent. PMID:28596686

Prevention of urinary tract infections in palliative radiation for vertebral metastasis and spinal compression: A pilot study in 71 patients

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

Manas, Ana; Glaria, Luis; Pena, Carmen

2006-03-01

Purpose: To assess the impact of bladder instillations of hyaluronic acid (HA) on the prevalence of urinary tract infection (UTI) in patients receiving emergency radiotherapy for metastatic spinal cord compression. Methods and Materials: Patients were recruited consecutively at one center and assigned to usual care (UC) (n = 34, mean age 62.2 years) or UC with once-weekly HA instillation (UC + HA) (Cystistat: 40 mg in 50 mL phosphate-buffered saline) (n = 37; mean age, 63.1 years). All patients had an indwelling catheter and received radiotherapy. UTI status was assessed at baseline and during hospitalization. Results: At baseline, patient groupsmore » were comparable, except for the prevalence of UTI at baseline, which was 11.8% and 0% in the UC and UC + HA patients, respectively (p = 0.0477). During hospitalization, 76.5% (vs. 11.8% at baseline, p < 0.0001) of the UC patients had a UTI compared with 13.5% (vs. 0% at baseline, p = 0.0541) of the UC + HA patients (p < 0.0001). Both groups were hospitalized for similar periods (19.8 days [UC] vs. 18.5 days, p = 0.4769) and received equivalent radiotherapy sessions (4.6 [UC] vs. 5.8 sessions, p = 0.2368). Conclusions: Patients receiving UC + HA had a 5.7-fold decrease in UTI prevalence over the hospitalization period compared to UC patients, suggesting that bladder instillations of HA effectively prevent UTI in patients with indwelling catheters receiving radiotherapy for nerve compression.« less

Mucosal Healing Is Associated With Improved Long-term Outcomes of Patients With Ulcerative Colitis: A Systematic Review and Meta-analysis.

PubMed

Shah, Shailja C; Colombel, Jean-Frederic; Sands, Bruce E; Narula, Neeraj

2016-09-01

The paradigm for treatment for ulcerative colitis (UC) is shifting from resolving symptoms toward objective measures such as mucosal healing (MH). However, it is unclear whether MH is associated with improved long-term outcomes. We performed a systematic review and meta-analysis to identify and analyze studies comparing long-term outcomes of patients with MH with those without MH. We performed a systematic search of 3 large databases to identify prospective studies of patients with active UC that included outcomes of patients found to have MH at the first endoscopic evaluation after initiation of UC therapy (MH1) compared with those without MH1. The primary outcome was clinical remission after at least 52 weeks. Secondary outcomes included proportions of patients who were free of colectomy or corticosteroids and rate of MH after at least 52 weeks. We analyzed 13 studies comprising 2073 patients with active UC. Patients with MH1 had pooled odds ratio of 4.50 for achieving long-term (after at least 52 weeks) clinical remission (95% confidence interval [CI], 2.12-9.52), 4.15 for remaining free of colectomy (95% CI, 2.53-6.81), 8.40 for achieving long-term MH (95% CI, 3.13-22.53), and 9.70 for achieving long-term corticosteroid-free clinical remission (95% CI, 0.94-99.67), compared with patients without MH1. We found no difference in outcomes if patients achieved MH1 while receiving biologic versus non-biologic therapy. In a meta-analysis, we associated MH with long-term clinical remission, avoidance of colectomy, and corticosteroid-free clinical remission. MH is therefore appropriate goal of UC therapy. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Takayasu's Disease in a Patient with Ulcerative Colitis.

PubMed

Chae, Myung Joon; Yu, Cheol Woong; Lee, Soo Yeon; Jang, Duck Hyun; Hyun, Joo Yong; Jeong, Su Jin; Kim, Myoung Hwan

2013-02-01

A 35-year-old Korean man with a 10-year history of ulcerative colitis (UC) presented with pain and swelling of the right neck. The patient was diagnosed with Takayasu's arteritis (TA) and had human leukocyte antigen (HLA) B-52, which is frequently found in patients having both UC and Takayasu's disease concurrently on HLA analysis. This case is the first report of a patient with both TA and UC in Korea, to the best of our knowledge.

Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy.

PubMed

Bank, S; Andersen, P S; Burisch, J; Pedersen, N; Roug, S; Galsgaard, J; Turino, S Y; Brodersen, J B; Rashid, S; Rasmussen, B K; Avlund, S; Olesen, T B; Hoffmann, H J; Nexø, B A; Sode, J; Vogel, U; Andersen, V

2018-01-01

Anti-tumour necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. A recent study indicated that genetically determined high activity of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6 and interferon gamma (IFN-γ), are associated with non-response to anti-TNF therapy. Using a candidate gene approach, 21 functional single-nucleotide polymorphisms (SNPs) in 14 genes in the Toll-like receptors, the inflammasome and the IFNG pathways were assessed in 482 and 256 prior anti-TNF naïve Danish patients with CD and UC, respectively. The results were analysed using logistic regression (adjusted for age and gender). Eight functional SNPs were associated with anti-TNF response either among patients with CD (TLR5 (rs5744174) and IFNGR2 (rs8126756)), UC (IL12B (rs3212217), IL18 (rs1946518), IFNGR1 (rs2234711), TBX21 (rs17250932) and JAK2 (rs12343867)) or in the combined cohort of patient with CD and UC (IBD) (NLRP3 (rs10754558), IL12B (rs3212217) and IFNGR1 (rs2234711)) (P<0.05). Only the association with heterozygous genotype of IL12B (rs3212217) (OR: 0.24, 95% CI: 0.11-0.53, P=0.008) among patients with UC withstood Bonferroni correction for multiple testing. In conclusion, Our results suggest that SNPs associated with genetically determined high activity of TLR5 among patients with CD and genetically determined high IL-12 and IL-18 levels among patients with UC were associated with non-response. Further studies will evaluate whether these genes may help stratifying patients according to the expected response to anti-TNF treatment.

Probiotics in the management of inflammatory bowel disease: a systematic review of intervention studies in adult patients.

PubMed

Jonkers, Daisy; Penders, John; Masclee, Ad; Pierik, Marieke

2012-04-16

Mounting evidence suggests an important role for the intestinal microbiota in the chronic mucosal inflammation that occurs in inflammatory bowel disease (IBD), and novel molecular approaches have further identified a dysbiosis in these patients. Several mechanisms of action of probiotic products that may interfere with possible aetiological factors in IBD have been postulated. Our objective was to discuss the rationale for probiotics in IBD and to systematically review clinical intervention studies with probiotics in the management of IBD in adults. A systematic search was performed in PubMed up to 1 October 2011, using defined keywords. Only full-text papers in the English language addressing clinical outcomes in adult patients were included. The 41 eligible studies were categorized on disease type (ulcerative colitis [UC] with/without an ileo-anal pouch and Crohn's disease [CD]) and disease activity. Pooled odds ratios were only calculated per probiotic for a specific patient group when more than one randomized controlled trial was available. Well designed randomized controlled trials supporting the application of probiotics in the management of IBD are still limited. Meta-analyses could only be performed for a limited number of studies revealing overall risk ratios of 2.70 (95% CI 0.47, 15.33) for inducing remission in active UC with Bifido-fermented milk versus placebo or no additive treatment (n = 2); 1.88 (95% CI 0.96, 3.67) for inducing remission in active UC with VSL#3 versus placebo (n = 2); 1.08 (95% CI 0.86, 1.37) for preventing relapses in inactive UC with Escherichia coli Nissle 1917 versus standard treatment (n = 3); 0.17 (95% CI 0.09, 0.33) for preventing relapses in inactive UC/ileo-anal pouch anastomosis (IPAA) patients with VSL#3 versus placebo; 1.21 (95% CI 0.57, 2.57) for preventing endoscopic recurrences in inactive CD with Lactobacillus rhamnosus GG versus placebo (n = 2); and 0.93 (95% CI 0.63, 1.38) for preventing endoscopic

Space Station UCS antenna pattern computation and measurement. [UHF Communication Subsystem

NASA Technical Reports Server (NTRS)

Hwu, Shian U.; Lu, Ba P.; Johnson, Larry A.; Fournet, Jon S.; Panneton, Robert J.; Ngo, John D.; Eggers, Donald S.; Arndt, G. D.

1993-01-01

The purpose of this paper is to analyze the interference to the Space Station Ultrahigh Frequency (UHF) Communication Subsystem (UCS) antenna radiation pattern due to its environment - Space Station. A hybrid Computational Electromagnetics (CEM) technique was applied in this study. The antenna was modeled using the Method of Moments (MOM) and the radiation patterns were computed using the Uniform Geometrical Theory of Diffraction (GTD) in which the effects of the reflected and diffracted fields from surfaces, edges, and vertices of the Space Station structures were included. In order to validate the CEM techniques, and to provide confidence in the computer-generated results, a comparison with experimental measurements was made for a 1/15 scale Space Station mockup. Based on the results accomplished, good agreement on experimental and computed results was obtained. The computed results using the CEM techniques for the Space Station UCS antenna pattern predictions have been validated.

Comparative analysis of inflamed and non-inflamed colon biopsies reveals strong proteomic inflammation profile in patients with ulcerative colitis

PubMed Central

2012-01-01

Background Accurate diagnostic and monitoring tools for ulcerative colitis (UC) are missing. Our aim was to describe the proteomic profile of UC and search for markers associated with disease exacerbation. Therefore, we aimed to characterize specific proteins associated with inflamed colon mucosa from patients with acute UC using mass spectrometry-based proteomic analysis. Methods Biopsies were sampled from rectum, sigmoid colon and left colonic flexure from twenty patients with active proctosigmoiditis and from four healthy controls for proteomics and histology. Proteomic profiles of whole colonic biopsies were characterized using 2D-gel electrophoresis, and peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for identification of differently expressed protein spots. Results A total of 597 spots were annotated by image analysis and 222 of these had a statistically different protein level between inflamed and non-inflamed tissue in the patient group. Principal component analysis clearly grouped non-inflamed samples separately from the inflamed samples indicating that the proteomic signature of colon mucosa with acute UC is strong. Totally, 43 individual protein spots were identified, including proteins involved in energy metabolism (triosephosphate isomerase, glycerol-3-phosphate-dehydrogenase, alpha enolase and L-lactate dehydrogenase B-chain) and in oxidative stress (superoxide dismutase, thioredoxins and selenium binding protein). Conclusions A distinct proteomic profile of inflamed tissue in UC patients was found. Specific proteins involved in energy metabolism and oxidative stress were identified as potential candidate markers for UC. PMID:22726388

Ultrasound for assessing disease activity in IBD patients: a systematic review of activity scores.

PubMed

Bots, S; Nylund, K; Löwenberg, M; Gecse, K; Gilja, O H; D'Haens, G

2018-04-19

Ultrasound (US) indices for assessing disease activity in IBD patients have never been critically reviewed. We aimed to systematically review the quality and reliability of available ultrasound (US) indices compared with reference standards for grading disease activity in IBD patients. Pubmed, Embase and Medline were searched from 1990 until June 2017. Relevant publications were identified through full text review after initial screening by 2 investigators. Data on methodology and index characteristics were collected. Study quality was assessed with a modified version of the Quadas-2 tool for risk of bias assessment. Of 20 studies with an US index, 11 studies met the inclusion criteria. Out of these 11 studies, 7 and 4 studied CD and UC activity indices, respectively. Parameters that were used in these indices included bowel wall thickness (BWT), Doppler signal (DS), wall layer stratification (WLS), compressibility, peristalsis, haustrations, fatty wrapping, contrast enhancement (CE) and strain pattern. Study quality was graded high in 5 studies, moderate in 3 studies and low in 3 studies. Ileocolonoscopy was used as the reference standard in 9 studies. In 1 study a combined index of ileocolonoscopy and barium contrast radiography and in 1 study histology was used as the reference standard. Only 5 studies used an established endoscopic index for comparison with US. Several US indices for assessing disease activity in IBD are available; however the methodology for development was suboptimal in most studies. For the development of future indices stringent methodological design is required.

20 CFR 603.23 - What information must State UC agencies obtain from other agencies, and crossmatch with wage...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false What information must State UC agencies obtain from other agencies, and crossmatch with wage information, for purposes of an IEVS? 603.23 Section 603.23 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR FEDERAL-STATE UNEMPLOYMENT COMPENSATION (UC) PROGRAM;...

Role of oral nitrate in the nitrosation of ( UC)proline by conventional microflora and germ-free rats

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

Mallett, A.K.; Rowland, I.R.; Walters, D.G.

1985-11-01

The urinary excretion of N-nitroso-L-(U- UC)proline by conventional microflora and germ free rats was used to assess the role of the gut bacteria and oral nitrate in the endogenous formation of N-nitroso compounds. The formation of nitrosoproline was qualitatively similar in conventional and germfree rats suggesting no involvement of the intestinal flora in this reaction. Furthermore, nitrosamino acid production was similar following the administration of nitrate and (U- UC)proline or (U- UC)proline alone, demonstrating no involvement of exogenous nitrate under the conditions of the experiment. Dietary contamination with nitrate/nitrite was negligible. The results are consistent with the suggestion that nitrate/nitritemore » reserves in the body are important in the formation of nitrosoproline in vivo.« less

The Individual Health Discount Rate in Patients with Ulcerative Colitis

PubMed Central

Waljee, Akbar K.; Morris, Arden M.; Waljee, Jennifer F.; Higgins, Peter D.R.

2015-01-01

Background In cost-effectiveness analysis, discount rates are used in calculating the value of future costs and benefits. However, standard discount rates may not accurately describe the decision-making of patients with Ulcerative Colitis (UC). These patients often choose the long-term risks of immunosuppressive therapy over the short-term risks of colectomy, demonstrating very high discount rates for future health. In this study, we aimed to measure the discount rate in UC patients and identify variables associated with the discount rate. Methods We surveyed patients with UC and patients who were post-colectomy for UC to measure their valuations of UC and colectomy health states. We used Standard Gamble(SG) and Time-Trade-Off(TTO) methods to assess current and future health state valuations, and calculated the discount rate. Results Participants included 150 subjects with UC and 150 subjects who were post-colectomy for UC. Discount rates varied widely (20.6%–100%) with an overall median rate of 55.0%, which was significantly higher than the standard rate of 5%. Older age and male gender and predicted high discount rates (aversion to immediate risk in favor of distant future risk). For each additional decade of age, patients’ expected discount rate increased by 0.77%. Female gender was the only predictor of very low discount rates. Female patients’ discount rates averaged 8.1% less than age-matched males. Conclusions The accepted discount rate of 5% grossly underestimates UC patients’ preference for long-term over short-term risk. This might explain UC patients’ frequent choice of the long-term risks of immunosuppressive medical therapy over the short-term risks of colectomy. PMID:21560195

UNIVERSITY OF CALIFORNIA – CENTER FOR ENVIRONMENTAL IMPLICATIONS OF NANOTECHNOLOGY (UC-CEIN)

EPA Science Inventory

EPA GRANT NUMBER: 0830117
Title: University of California – Center for Environmental Implications of Nanotechnology (UC-CEIN)
Investigator: Andre E. Nel
Institution: University of California - Los Angeles
EPA Project Officer: Nor...

Interleukin 1 β (IL-1B) and IL-1 antagonist receptor (IL-1RN) gene polymorphisms are associated with the genetic susceptibility and steroid dependence in patients with ulcerative colitis.

PubMed

Yamamoto-Furusho, Jesús K; Santiago-Hernández, Jean J; Pérez-Hernández, Nonanzit; Ramírez-Fuentes, Silvestre; Fragoso, José Manuel; Vargas-Alarcón, Gilberto

2011-07-01

Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. Among cytokines induced in UC, interleukin 1 antagonist (IL-1ra) and interleukin 1 β (IL-1β) seems to have a central role because of its immunoregulatory and proinflammatory activities. To determine the association between IL-1RA and IL-1B gene polymorphisms and the clinical features of UC in the Mexican Mestizo population. Five polymorphisms in the IL-1 gene cluster members IL-1B (rs16944), IL1F10 (rs3811058), and IL-1RN (rs419598, rs315952, and rs315951) were genotyped by 5' exonuclease TaqMan genotyping assays in a group of 200 Mexican patients with UC and 248 ethnically matched unrelated healthy controls. We found a significant increased frequencies of IL-1RN6/1 TC (rs315952) and RN6/2 CC (rs315951) and decreased frequency of IL-1B-511 TC (rs16944) genotypes in UC patients as compared with healthy controls. In the subgroup analysis, we found a significant association between the RN6/2 GG (rs315951) and IL-1B-511 CC (rs16944) genotypes and the presence of steroid-dependence in UC patients (pC=00001, OR=15.6 and pC=0.008, OR=4.09, respectively). Patients with UC showed increased frequencies of IL-1RN "CTC" and "TCG" haplotypes when compared with healthy controls (P=0.019, OR=1.43 and P<10(-7), OR=2.63, respectively). Two haplotypes (TTG and CTG) showed decreased frequency in patients when compared with healthy controls (P=9×10(-7), OR=0.11 and P=8×10(-6), OR=0.11, respectively). IL-1 RN and IL-1B polymorphisms were associated with the genetic susceptibility to develop UC and might be associated with the presence of steroid-dependence in UC patients.

EOP and SAA Undergraduates Who Left UC Davis without a Degree.

ERIC Educational Resources Information Center

Rasor, Marianne

Undergraduate students enrolled in the Educational Opportunity Program (EOP) or the Student Affirmative Action (SAA) program at the University of California (UC), Davis, who withdrew before graduation were surveyed in 1981. Attention was directed to the respondents' educational experiences after leaving, their current employment, and their…

LncRNA uc.48+ is involved in the diabetic immune and inflammatory responses mediated by P2X7 receptor in RAW264.7 macrophages.

PubMed

Wu, Hong; Wen, Fang; Jiang, Mei; Liu, Qiang; Nie, Yijun

2018-08-01

High glucose combined with high FFAs can contribute to the unfavorable development of type 2 diabetes mellitus (T2DM) and monocytes/macrophages are important in the occurrence and development of T2DM, which is regarded as a type of low‑grade inflammation. Although our previous study demonstrated that increased expression of P2X7 receptor (P2X7R) in peripheral blood monocytes may alter the innate immune system and that long non‑coding (lnc)RNA uc.48+ was involved in diabetic neuropathic pain, the involvement of uc.48+ mediated by the P2X7R in monocyte/macrophages during T2DM has not been reported. In the present study, the effectsof uc.48+ small interference RNA (siRNA) on factors, including the mRNA and protein expression of P2X7R, apoptosis and proliferation, levels of reactive oxygen species (ROS), cytokine levels, and expression of phosphorylated (p‑) extracellular signal‑regulated kinase (ERK)1/2, were examined in RAW264.7 macrophages following exposure to high glucose and high plasma free fatty acids (FFAs). After RAW264.7 cells were transfected with uc.48+ siRNA under high glucose conditions and FFAs treatment, the mRNA expression levels of uc.48+ and P2X7 receptor were detected by reverse transcription‑polymerase chain reaction. The protein mass of P2X7 receptor and ERK signaling pathway were assessed by western blotting. ROS and calcium concentrations, and culture supernatant cytokine content [tumor necrosis factor‑α, interleukin (IL)‑10, IL‑1β] were detected by fluorescent probes and ELISA respectively. Cell viability and apoptosis were determined by MTS test and flow cytometry, respectively. It was found that treatment of RAW264.7 cells with high glucose and FFAs, which exhibited increased expression of uc.48+, evoked P2X7R‑mediated immune and inflammatory responses through several means, including cytokine secretion, ROS formation, and activation of the ERK signaling pathway. The uc.48+ siRNA regulated these factors and thus

Patients' diets and preferences in a pediatric population with inflammatory bowel disease.

PubMed

Green, T J; Issenman, R M; Jacobson, K

1998-01-01

To determine the dietary practices of the pediatric inflammatory bowel disease population at the Children's Hospital of the Hamilton Health Sciences Corporation and the reported effectiveness of those diets. A questionnaire mailed to 153 pediatric patients was returned by 125 patients (76 Crohn's disease [CD] and 49 ulcerative colitis [UC] patients)--an 82% response rate. The median age of respondents was 13 years, and 62% were male. Ninety per cent and 71% of CD and UC patients, respectively, had changed their diets since diagnosis. Caloric supplements (eg, BOOST [Mead Johnson Nutritionals]), sole source nutrition, low fibre and lactose-free diets were used by more than 15% of CD patients, whereas lactose-free, nonspicy, low acid, additive-free, caloric supplement and low fibre diets were used by more than 15% of UC patients. A diet supplement was more commonly used in CD patients (P < 0.05) and an additive-free diet in UC patients. Corn and corn products, nuts, milk and bran were avoided by more than 20% of CD and UC patients; however, more CD than UC patients avoided corn and corn products. In addition, UC patients (more than 20%) also avoided tomato, other dairy (nonfluid milk-based products and foods containing milk products), chocolate, cheese, wheat, tomato sauces and fruit juice. A benefit was reported for 103 of 141 reported diets, with the most commonly alleviated symptoms being abdominal pain, diarrhea and flatulence. Many children with inflammatory bowel disease have altered their diets to manage their disease and have attributed symptomatic relief to these diets.

Prevalence and risk factors for colorectal adenomas in patients with ulcerative colitis.

PubMed

Gordillo, Jordi; Zabana, Yamile; Garcia-Planella, Esther; Mañosa, Míriam; Llaó, Jordina; Gich, Ignasi; Marín, Laura; Szafranska, Justyna; Sáinz, Sergio; Bessa, Xavier; Cabré, Eduard; Domènech, Eugeni

2018-03-01

Patients with ulcerative colitis (UC) have an increased risk of colorectal cancer. Scarce data regarding the development of adenomas in these patients are available both for normal and colitic mucosa. The objective of this article is to evaluate the prevalence of adenomatous polyps and associated risk factors in patients with UC. Patients with UC were identified from the databases of two tertiary referral centers. Medical, endoscopic and histologic reports were reviewed. A total of 403 patients were included (53% male; 33% extensive colitis) and 1065 colonoscopies (median per patient, 2) were recorded and analyzed. Seventy-four adenomas in 47 patients (11.7%) and three cases of colorectal cancer were found during a median follow-up of 6.3 years. The cumulative risk of colorectal adenoma was 4.7%, 16.7%, 23.6% and 34.4% at 10, 20, 30 and 40 years from UC diagnosis, respectively. The cumulative risk of developing metachronous colorectal adenoma was 66.7%, 87.9%, and 90.9% at 5, 10, and 15 years from first adenoma detection. Older age at UC diagnosis and longer disease duration were independent risk factors for colorectal adenoma development. The prevalence of colorectal adenomas among UC patients seems to be higher than previously reported, although lower than in the background population.

Anemia at the time of diagnosis of inflammatory bowel disease: Prevalence and associated factors in adolescent and adult patients.

PubMed

Lucendo, Alfredo J; Arias, Ángel; Roncero, Óscar; Hervías, Daniel; Verdejo, Cristina; Naveas-Polo, Carmen; Bouhmidi, Abdelmouneim; Lorente, Rufo; Alcázar, Luis Miguel; Salueña, Irina; García-Quiñones, Julio A; Carrillo-Ramos, María Jesús

2017-04-01

The prevalence, characteristic and determinants of anemia, at the time of inflammatory bowel disease (IBD) diagnosis have yet to be fully elucidated. Retrospective cross-sectional study. Analytical data and disease characteristics obtained upon diagnosis of 1278 IBD patients [Crohn's disease/ulcerative colitis (CD/UC): 718/560] were collected. Anemia was present in 41.2% of patients at diagnosis (47% and 33.8% of CD and UC patients, respectively; p<0.001), being severe in 5.5%. Iron deficiency anemia represented 69.6% of cases, with no differences between CD and UC. Female sex was the strongest risk factor for anemia in both CD and UC (OR 7.11; 95%CI 4.18-12.10 and 6.55; 95%CI 3.39-12.63, respectively), followed by elevated (≥2mg/dL) C-reactive protein (OR 4.08; 95%CI 2.39-6.97 and 4.58; 95%CI 2.26-9.27, respectively). Current smoking was a risk factor for anemia in CD (OR 2.23; 95%CI 1.24-4.02), but a protective one in UC (OR 0.36; 95%CI 0.14-0.92). A penetrating CD behavior increased the risk of anemia (OR 3.34; 95%CI 1.36-8.21); in UC, anemia increased with disease extension (E2+E3) (OR 1.80; 95%CI 1.13-2.86). Female sex and disease activity are major determinants of anemia at IBD diagnosis. Anemia is associated with disease behavior in CD and with disease extension in UC. Copyright © 2016. Published by Elsevier Ltd.

Effects of defoliation in the developing leaf zone on young Populus Xeuramericana plants. II. Distribution of UC-photosynthate after defoliation

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

Bassman, J.H.; Dickmann, D.I.

Patterns of UC-photosynthate distribution in growth chamber-grown Populus xeuramericana cv. Negrito de Granada were determined 24 h, 3 weeks, and 5 weeks after defoliation in the developing leaf zone. Translocation patterns were determined by exposing leaves below, within, or above the defoliated zone to UCO2 and determining UC distribution within the plant after 48 h. Translocation patterns were altered within 24 h after defoliation. When leaves below or remaining tissue of leaves within the zone of defoliation were exposed to UCO2, a greater percentage of UC-photosynthate was transported to the expanding shoot and lateral branches and less to the rootsmore » in defoliated plants compared to controls. Little difference between defoliated and control plants and UC distribution occurred when new leaves produced subsequent to defoliation were exposed to UCO2. By 5 weeks after defoliation there was little difference in patterns of UC distribution between defoliated and control plants. These results substantiate biomass partitioning data which showed that a single defoliation of young poplar plants did not affect diameter or height growth, whereas leaf growth was stimulated and root growth reduced.« less

Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer.

PubMed

Mijwel, Sara; Cardinale, Daniele A; Norrbom, Jessica; Chapman, Mark; Ivarsson, Niklas; Wengström, Yvonne; Sundberg, Carl Johan; Rundqvist, Helene

2018-05-11

Exercise has been suggested to ameliorate the detrimental effects of chemotherapy on skeletal muscle. The aim of this study was to compare the effects of different exercise regimens with usual care on skeletal muscle morphology and mitochondrial markers in patients being treated with chemotherapy for breast cancer. Specifically, we compared moderate-intensity aerobic training combined with high-intensity interval training (AT-HIIT) and resistance training combined with high-intensity interval training (RT-HIIT) with usual care (UC). Resting skeletal muscle biopsies were obtained pre- and postintervention from 23 randomly selected women from the OptiTrain breast cancer trial who underwent RT-HIIT, AT-HIIT, or UC for 16 wk. Over the intervention, citrate synthase activity, muscle fiber cross-sectional area, capillaries per fiber, and myosin heavy chain isoform type I were reduced in UC, whereas RT-HIIT and AT-HIIT were able to counteract these declines. AT-HIIT promoted up-regulation of the electron transport chain protein levels vs. UC. RT-HIIT favored satellite cell count vs. UC and AT-HIIT. There was a significant association between change in citrate synthase activity and self-reported fatigue. AT-HIIT and RT-HIIT maintained or improved markers of skeletal muscle function compared with the declines found in the UC group, indicating a sustained trainability in addition to the preservation of skeletal muscle structural and metabolic characteristics during chemotherapy. These findings highlight the importance of supervised exercise programs for patients with breast cancer during chemotherapy.-Mijwel, S., Cardinale, D. A., Norrbom, J., Chapman, M., Ivarsson, N., Wengström, Y., Sundberg, C. J., Rundqvist, H. Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer.

[Catalase gene rs1001179 polymorphism and oxidative stress in patients with chronic hepatitis C and ulcerative colitis].

PubMed

Bulatova, I A; Tretyakova, Yu I; Shchekotov, V V; Shchekotova, A P; Ulitina, P V; Krivtsov, A V; Nenasheva, O Yu

2015-01-01

To study the rs1001179 polymorphism of the catalase (CAT) gene and to estimate the serum levels of the enzymes catalase and glutathione peroxidase (GP) in patients with chronic hepatitis C (CHC) and in those with ulcerative colitis (UC) in the Perm Territory. Ninety patients with reactivation-phase CHC and 50 patients with exacerbation-phase UC were examined. The serum levels of catalase and GP were determined and the polymorphic variants of the marker of CAT gene rs1001179 in the DNA isolated from whole blood were found in all the patients. In the CHC and UC groups, the levels of catalase and GP were found to be lower than that in apparently healthy individuals. Furthermore, both groups showed a direct correlation between the activities of the enzymes. In the patients with CHC and in those with UC, the spread of genotypes and alleles generally failed to virtually differ from that in the control group. The G/G genotype was prevalent in all the groups. In the patients with CHC, the minor A allele demonstrated a significant inverse correlation with the enzyme catalase (r = -0.16; p = 0.02) and GP (r = -0.13; p = 0.047). The lower serum levels of catalase and GP are indicative of oxidative stress in the patients with CHC or UC. In the patients with CHC, the significant correlation of the pathological rs1701179 A allele marker with the processes of synthesis of antioxidant enzymes may suggest that CAT gene polymorphism in the A/A homozygotes might affect the regulation mechanism involved in the antioxidant system in the liver.

Mucosal CXCR4+ IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14 macrophage activation.

PubMed

Uo, Michihide; Hisamatsu, Tadakazu; Miyoshi, Jun; Kaito, Daiki; Yoneno, Kazuaki; Kitazume, Mina T; Mori, Maiko; Sugita, Akira; Koganei, Kazutaka; Matsuoka, Katsuyoshi; Kanai, Takanori; Hibi, Toshifumi

2013-12-01

Chronic inflammation characterised by IgG-producing plasma cell infiltration of colonic mucosa is a histological hallmark of ulcerative colitis (UC); however, whether its function is pathogenic or protective remains unclear. To explore the contribution of intestinal IgG plasma cells to UC pathogenesis. We isolated lamina propria mononuclear cells (LPMCs) from intestinal mucosa of UC patients and analysed the characteristics of intestinal plasma cells (expression profiles of differentiation molecules and chemokine receptors). We investigated the involvement of IgG-immune complex (IC)-Fc gamma receptor (FcγR) signalling in intestinal inflammation by examining the cytokine production by LPMCs in response to IgG-IC stimulation. IgG plasma cells that were markedly increased in number in the inflamed mucosa of UC patients showed a distinct expression profile (CD19(+)CD27(low), CCR10(low)CXCR4(high)) compared with IgA plasma cells (CD19(+/-)CD27(high), CCR10(high)CXCR4(-/low)). In vitro IgG-IC stimulation activated intestinal CD14 macrophages that were increased in number in the inflamed mucosa of UC patients via FcγRI and FcγRII, and induced the extensive production of pro-inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin-1β (IL-1β), comparable to the effect of commensal bacteria stimulation. Co-stimulation with IgG-IC and commensal bacteria increased TNF and IL-1β production more than stimulation with the latter alone. Furthermore, IgG-IC notably up-regulated the expression of TL1A, whereas commensal bacteria specifically induced IL-23. Collectively, these results demonstrate a novel aspect of UC pathogenesis in which unique IgG plasma cells infiltrate the inflamed mucosa via CXCR4, and critically influence UC pathogenesis by exacerbating mucosal inflammation through the activation of 'pathogenic' intestinal CD14 macrophages via IgG-IC-FcγR signalling.

[The impact of stress and personality on resilience of patients with ulcerative colitis].

PubMed

Liu, W; Wang, J; Wang, H; Chen, X Y; Li, J S

2018-02-01

Objective: To study relevant factors that influence psychological resilience in patients with ulcerative colitis(UC), especially the role of perceived stress and personality. Methods: Patients with UC were recruited from January 2015 to December 2016 in the First Hospital of Zhengzhou University. Education levels, income, duration of disease, Mayo score and disease phenotype according to Montreal classification were collected. Resilience was measured using Connor-Davidson resilience scale (CD-RISC). Perceived stress was measured by perceived stress scale (PSS). Personality was evaluated using Eysenck personality questionnaire (EPQ). Univariate analyses were conducted to determine the correlation of variables with resilience and thereafter those statistically significant were reanalyzed via a multivariate regression model. Results: A total of 188 patients with UC were finally recruited. Univariate analyses demonstrated resilience was inversely associated with perceived stress, Mayo score and neuroticism. Extraversion, income, college education were positively related to resilience. However, multivariate analyses revealed that perceived stress( OR= 0.901, 95% CI 0.833-0.975), extraversion ( OR= 1.257, 95% CI 1.087-1.454), neuroticism ( OR= 0.818, 95% CI 0.679-0.985), Mayo score ( OR= 0.856, 95% CI 0.742-0.988) and income ( OR= 6.411, 95% CI 2.136-9.244) were significantly related to resilience. Conclusions: Resilience of UC patients is not only associated with disease activity, but also with personality, perceived stress and income.

Determination of Cytomegalovirus Prevalence and Glycoprotein B Genotypes Among Ulcerative Colitis Patients in Ahvaz, Iran

PubMed Central

Taherkhani, Reza; Farshadpour, Fatemeh; Makvandi, Manoochehr; Hamidifard, Mojtaba; Esmailizadeh, Mahdi; Ahmadi, Bijan; Heidari, Hamid

2015-01-01

Background: The human cytomegalovirus (HCMV) is a common pathogen which usually remains asymptomatic in the healthy adults; however, it can cause a symptomatic disease in the immunocompromised patients. The risk of infection with HCMV increases in ulcerative colitis (UC) patients as a result of receiving immunosuppressive agents. Objectives: This study aimed to determine the prevalence and the glycoprotein B genotypes of HCMV among the patients with HCMV disease superimposed on an UC flare that required hospitalization in Imam Khomeini Hospital in Ahvaz, Iran, during 2010- 2012. Patients and Methods: In this case-control study, formalin-fixed paraffin-embedded intestinal tissue samples were taken from 98 patients with UC disease including 53 males and 45 females (mean age ± standard deviation, 38.95 ± 17.93) and 67 control patients with noninflammatory disease who were referred to Imam Khomeini Hospital during 2010-2012. Detection of HCMV genome in intestinal samples was carried out by seminested polymerase chain reaction. Glycoprotein B genotypes were determined by sequencing. Results: Among 98 patients with UC, only 12 (12.2%) patients were positive for HCMV genome, while the HCMV genome was not detected in any of the controls. (P = 0.002). The distribution of HCMV gB genotypes in 12 CMV-positive UC patients was as follow: gB1, 11 (91.7%) and gB3, 1 (8.3%). The most prevalent genotype in CMV-positive UC patients was gB1. Conclusions: In this study, high prevalence of 91.7% HCMV gB1 genotype was predominant among HCMV-positive UC patients, which suggests that there might be an association between HCMV gB genotype 1 and UC disease. PMID:25793098

Effectiveness and Safety of Vedolizumab Induction Therapy for Patients With Inflammatory Bowel Disease.

PubMed

Amiot, Aurelien; Grimaud, Jean-Charles; Peyrin-Biroulet, Laurent; Filippi, Jerome; Pariente, Benjamin; Roblin, Xavier; Buisson, Anthony; Stefanescu, Carmen; Trang-Poisson, Caroline; Altwegg, Romain; Marteau, Philippe; Vaysse, Thibaud; Bourrier, Anne; Nancey, Stephane; Laharie, David; Allez, Matthieu; Savoye, Guillaume; Moreau, Jacques; Gagniere, Charlotte; Vuitton, Lucine; Viennot, Stephanie; Aubourg, Alexandre; Pelletier, Anne-Laure; Bouguen, Guillaume; Abitbol, Vered; Bouhnik, Yoram

2016-11-01

Phase 3 trials have shown the efficacy of vedolizumab, which binds to integrin α4β7, in patients with Crohn's disease (CD) or ulcerative colitis (UC). We investigated the effectiveness and safety of vedolizumab in patients who failed anti-tumor necrosis factor therapy. From June through December 2014, there were 173 patients with CD and 121 patients with UC who were included in a multicenter nominative compassionate early access program granted by French regulatory agencies. This program provided patients with access to vedolizumab before it was authorized for marketing. Vedolizumab (300 mg) was administered intravenously at weeks 0, 2, and 6, and then every 8 weeks. Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. We report results obtained after the 14-week induction phase. Among the 294 patients treated with vedolizumab (mean age, 39.5 ± 14.0 y; mean disease duration, 10.8 ± 7.6 y; concomitant steroids, 44% of cases), 276 completed the induction period, however, 18 discontinued vedolizumab because of a lack of response (n = 14), infusion-related reaction (n = 2), or infections (n = 2). At week 14, 31% of patients with CD were in steroid-free clinical remission and 51% had a response; among patients with UC, 36% were in steroid-free clinical remission and 50% had a response. No deaths were reported. Severe adverse events occurred in 24 patients (8.2%), including 15 (5.1%) that led to vedolizumab discontinuation (1 case of pulmonary tuberculosis and 1 rectal adenocarcinoma). In a cohort of patients with CD or UC who failed previous anti-tumor necrosis factor therapy, approximately one third of patients achieved steroid-free clinical remission after 14 weeks of induction therapy with vedolizumab. This agent had an acceptable safety profile in these patients. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Fatty acyltranferases in serum in cystic fibrosis (CF) patients

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

Zielenski, J.; Newman, L.J.; Slomiany, B.L.

1987-05-01

Studies on serum and gastrointestinal secretion from CF patient is suggest that defective accumulation of mucus in gastrointestinal tract and excessive amount of a protease resistant peptides in serum are related to the abnormal activity of enzymes responsible for fatty acylation of proteins. Here, the authors investigated the fatty acyltransferase activities in serum of normal and CF patients. A 15 l of serum was mixed with 0.85 nmol ( UC)palmitoyl CoA, 200 g of serine and threonine and incubated at 37C for 30 min. The incubates were immediately frozen, dried extracted with C/M and chromatographed in chloroform/methanol/water. The incorporation ofmore » ( UC)palmitate was determined using linear radioscanner and authoradiography. The results of HPTLC revealed that CF serum in addition of ACAT and LCAT contained enzymes responsible for the transfer of ( UC)palmitate to monoacylphosphoglycerides, and serine and threonine. In normal serum the formation of a small amount of palmitoyl serine and palmitoyl threonine was also observed but the acylation of monoacylphosphoglycerides was not detectable. The authors conclude that in cystic fibrosis the abnormal fatty acyltransferases are responsible for the occurrence of protease resistant glycoprotein, unusual peptides in serum and possibly for the modification of membrane proteins and lipids.« less

Immunosuppressive function of mesenchymal stem cells from human umbilical cord matrix in immune thrombocytopenia patients.

PubMed

Ma, Li; Zhou, Zeping; Zhang, Donglei; Yang, Shaoguang; Wang, Jinhong; Xue, Feng; Yang, Yanhui; Yang, Renchi

2012-05-01

Human umbilical cord matrix/Wharton's jelly (hUC)-derived mesenchymal stem cells (MSC) have been shown to have marked therapeutic effects in a number of inflammatory diseases and autoimmune diseases in humans based on their potential for immunosuppression and their low immunogenicity. Currently, no data are available on the effectiveness of UC-MSC transplantation in immune thrombocytopenia (ITP) patients. It was the objective of this study to assess the effect of allogeneic UC-MSCs on ITP patients in vitro and in vivo. Peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BM-MNCs) from ITP patients and healthy controls were co-cultured with UC-MSCs for three days and seven days, respectively. Flow cytometry and ELISA were applied to assess the various parameters. In PBMCs from ITP patients, the proliferation of autoreactive T, B lymphocytes and destruction of autologous platelets were dramatically suppressed by UC-MSCs. UC-MSCs not only suppressed co-stimulatory molecules CD80, CD40L and FasL expression but also in shifting Th1/Th2/Treg cytokines profile in ITP patients. UC-MSCs obviously reversed the dysfunctions of megakaryocytes by promoting platelet production and decreasing the number of living megakaryocytes as well as early apoptosis. In addition, the level of thrombopoietin was increased significantly. Our clinical study showed that UC-MSCs play a role in alleviating refractory ITP by increasing platelet numbers. These findings suggested that UC-MSCs transplantation might be a potential therapy for ITP.

Vedolizumab Treatment for Ulcerative Colitis in an Elderly Multimorbid Patient with Hemophilia A.

PubMed

Schäffler, Holger; Huth, Astrid; Lamprecht, Georg; Anders, Olaf

2017-01-01

The treatment of inflammatory bowel diseases (IBD) can be challenging, especially in elderly multimorbid patients. Since incidence and prevalence rates of IBD are rising steadily, treatment of older patients with relevant and also rare comorbidities will be of increasing relevancy for caregivers. Here we report on a 74-year-old multimorbid patient with severe ulcerative colitis (UC) and hemophilia A. Because of the chronic active disease, therapy with a tumor necrosis factor-α inhibitor was started. He suffered from a severe infectious complication (pneumonia) under therapy with infliximab. The therapy was changed to vedolizumab, with which the patient stayed in long-term clinical and endoscopic remission. Because the patient had a non-ST-segment elevation myocardial infarction in April 2016, he received dual platelet inhibitor therapy with aspirin and clopidogrel. Because of consecutive aspirin intolerance, the therapy was changed to clopidogrel monotherapy. Although the UC was treated appropriately with vedolizumab and the patient was in endoscopic mucosal remission, recurrent bleeding episodes from multiple inflammatory pseudopolyps occurred. The bleeding episodes resolved quickly after immediate treatment with factor VIII (Kogenate®). In conclusion, we describe the first patient in the literature with UC and hemophilia A who stayed in long-term remission under therapy with vedolizumab. From our point of view, vedolizumab can be safely administered in the setting of UC and hemophilia A. Antiplatelet drugs which inhibit primary hemostasis must be used with caution in this setting. Bleeding episodes can be treated safely and effectively with factor VIII (Kogenate®).

Squamous cell dysplasia in the proximal rectum of three patients treated for ulcerative colitis on immunomodulators.

PubMed

Connolly, James G; Goldstone, Stephen E

2017-05-01

Anal canal high-grade squamous intraepithelial lesion (HSIL) is the precursor to anal cancer. Immunocompromised patients are at increased risk and disease is usually within 3 cm from the anal verge. High-resolution anoscopy (HRA) with an 8-cm anoscope is used to identify and guide cautery treatment of HSIL. We report three patients with a long-term history of ulcerative colitis (UC) treated with systemic immunomodulators who developed proximally located rectal HSIL. Two patients were HIV-negative women, 63 and 48 years old, and the third was a 51-year-old HIV-positive man with underlying UC for 10, 16, and 3 years, respectively. They each presented with a HPV-positive HSIL visibly extending above the limits of the anoscope used for HRA. None developed cancer. All had episodes of active UC. It is unclear what causative role systemic immunomodulators play in predisposing UC patients to proximal HSIL. HSIL probably developed on a tongue of HPV-infected squamous epithelium growing proximally over the inflamed rectum. Islands developed when areas of squamous epithelium degenerated, creating skip areas. This study highlights the potential for HSIL to extend into the rectum either as a contiguous patch or isolated islands and the need for heightened surveillance in patients with extensive anal canal HSIL treated with immunodulator therapy. HSIL identified at the limit of the anoscope should be investigated further with colonoscopy, and argon plasma coagulation (APC) ablation can serve as an effective treatment option. Patients are at risk for stricture, but it is unclear what role the UC or the ablation played in stricture formation.

Prevalence and risk factors for colorectal adenomas in patients with ulcerative colitis

PubMed Central

Gordillo, Jordi; Zabana, Yamile; Garcia-Planella, Esther; Mañosa, Míriam; Llaó, Jordina; Gich, Ignasi; Marín, Laura; Szafranska, Justyna; Sáinz, Sergio; Bessa, Xavier; Cabré, Eduard; Domènech, Eugeni

2018-01-01

Background Patients with ulcerative colitis (UC) have an increased risk of colorectal cancer. Scarce data regarding the development of adenomas in these patients are available both for normal and colitic mucosa. Objective The objective of this article is to evaluate the prevalence of adenomatous polyps and associated risk factors in patients with UC. Methods Patients with UC were identified from the databases of two tertiary referral centers. Medical, endoscopic and histologic reports were reviewed. Results A total of 403 patients were included (53% male; 33% extensive colitis) and 1065 colonoscopies (median per patient, 2) were recorded and analyzed. Seventy-four adenomas in 47 patients (11.7%) and three cases of colorectal cancer were found during a median follow-up of 6.3 years. The cumulative risk of colorectal adenoma was 4.7%, 16.7%, 23.6% and 34.4% at 10, 20, 30 and 40 years from UC diagnosis, respectively. The cumulative risk of developing metachronous colorectal adenoma was 66.7%, 87.9%, and 90.9% at 5, 10, and 15 years from first adenoma detection. Older age at UC diagnosis and longer disease duration were independent risk factors for colorectal adenoma development. Conclusions The prevalence of colorectal adenomas among UC patients seems to be higher than previously reported, although lower than in the background population. PMID:29511562

Determination of cytomegalovirus prevalence and glycoprotein B genotypes among ulcerative colitis patients in ahvaz, iran.

PubMed

Taherkhani, Reza; Farshadpour, Fatemeh; Makvandi, Manoochehr; Hamidifard, Mojtaba; Esmailizadeh, Mahdi; Ahmadi, Bijan; Heidari, Hamid

2015-02-01

The human cytomegalovirus (HCMV) is a common pathogen which usually remains asymptomatic in the healthy adults; however, it can cause a symptomatic disease in the immunocompromised patients. The risk of infection with HCMV increases in ulcerative colitis (UC) patients as a result of receiving immunosuppressive agents. This study aimed to determine the prevalence and the glycoprotein B genotypes of HCMV among the patients with HCMV disease superimposed on an UC flare that required hospitalization in Imam Khomeini Hospital in Ahvaz, Iran, during 2010- 2012. In this case-control study, formalin-fixed paraffin-embedded intestinal tissue samples were taken from 98 patients with UC disease including 53 males and 45 females (mean age ± standard deviation, 38.95 ± 17.93) and 67 control patients with noninflammatory disease who were referred to Imam Khomeini Hospital during 2010-2012. Detection of HCMV genome in intestinal samples was carried out by seminested polymerase chain reaction. Glycoprotein B genotypes were determined by sequencing. Among 98 patients with UC, only 12 (12.2%) patients were positive for HCMV genome, while the HCMV genome was not detected in any of the controls. (P = 0.002). The distribution of HCMV gB genotypes in 12 CMV-positive UC patients was as follow: gB1, 11 (91.7%) and gB3, 1 (8.3%). The most prevalent genotype in CMV-positive UC patients was gB1. In this study, high prevalence of 91.7% HCMV gB1 genotype was predominant among HCMV-positive UC patients, which suggests that there might be an association between HCMV gB genotype 1 and UC disease.

Risk of colectomy in patients with ulcerative colitis under thiopurine treatment.

PubMed

Cañas-Ventura, Alex; Márquez, Lucia; Ricart, Elena; Domènech, Eugeni; Gisbert, Javier P; García-Sanchez, Valle; Marín-Jiménez, Ignacio; Rodriguez-Moranta, Francisco; Gomollón, Fernando; Calvet, Xavier; Merino, Olga; Garcia-Planella, Esther; Vázquez-Romero, Narcis; Esteve, Maria; Iborra, Marisa; Gutiérrez, Ana; Vera, Maribel; Andreu, Montserrat

2014-10-01

Little is known about the risk factors of colectomy in patients with ulcerative colitis (UC) under thiopurine treatment. The aim of the study was to determine the prevalence and the predictive risk factors of colectomy in an extensive cohort of patients with UC treated with thiopurines in Spain. Among 5753 UC patients, we identified those diagnosed between 1980 and 2009 and treated with azathioprine or mercaptopurine (AZA/MP). We analyzed the age at diagnosis, familial history of IBD, extraintestinal manifestations (EIMs), disease extent, smoking status and treatment requirements (AZA/MP, cyclosporine (CsA) or anti-TNFα). Colectomies for dysplasia or cancer were excluded. Survival analysis and Cox proportional hazard regression were performed. Results were reported as hazard ratios (HR) with 95% CI. Among the 1334 cases included, 119 patients (8.9%) required colectomy after a median time of 26 months (IQR 12-42) after AZA/MP initiation. Independent predictors of colectomy were: Extensive UC (HR 1.7, 95% CI: 1.1-2.6), EIMs (HR 1.5, 95% CI: 1.0-2.4), need for antiTNFα (HR 2.3, 95% CI: 1.5-3.4) and need for CsA (HR 2.4, 95% CI: 1.6-3.7). Patients requiring early introduction of AZA/MP had an increased risk of colectomy with a HR of 4.9 (95% CI: 3.2-7.8) when AZA/MP started in the first 33 months after UC diagnosis. Nearly one-tenth of patients with UC under thiopurines require colectomy. Extensive UC, EIMs, need for CsA or anti-TNFα ever and an early need for AZA/MP treatment were associated with a higher risk of colectomy. These risk factors of colectomy could help to stratify risk in further controlled studies in UC. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Surgical Outcomes in Vedolizumab-Treated Patients with Ulcerative Colitis.

PubMed

Lightner, Amy L; McKenna, Nicholas P; Moncrief, Sara; Pemberton, John H; Raffals, Laura E; Mathis, Kellie L

2017-12-01

Surgical outcomes and pouch outcomes in the setting of vedolizumab remains poorly understood. We sought to determine the rate of 30-day postoperative surgical infectious complications and pouch-specific complications among patients with ulcerative colitis (UC) who received vedolizumab within 12 weeks of surgery. A retrospective chart review between 5/1/2014 and 12/31/2016 of all adult patients with UC who underwent an abdominal operation was performed. Patients with UC who received vedolizumab within 12 weeks of their abdominal operation were compared with patients with UC on anti-TNFα treatment. Eighty-eight patients received vedolizumab and 62 received anti-TNFα within 12 weeks of surgery. More vedolizumab-treated patients had superficial surgical site infections (P = 0.047) and mucocutaneous separation at the ileostomy (P = 0.047), but there was no difference in the overall surgical infectious complication rate, deep space SSI, 30-day hospital readmission or return to the operating room. On univariate analysis of SSI among patients with UC, exposure to vedolizumab was not a significant predictor of SSI (P = 0.27), but steroids were predictive of SSI on univariate (P = 0.02) and multivariable analysis (P = 0.02). After ileal pouch anal anastomosis, there was a higher rate of intra-abdominal abscesses (31.3% versus 5.9%) and mucocutaneous separation (18.8% versus 0%) in the vedolizumab group compared with the anti-TNFα group, but statistical significance was not reached. Vedolizumab patients had significantly increased rates of superficial SSI, but not overall infectious complications. Among ileal pouch anal anastomosis patients, peripouch abscess rates were increased among vedolizumab-treated patients, but this did not reach statistical significance. Vedolizumab seems safe in the perioperative period for patients with UC.

When should ulcerative colitis patients undergo colectomy for dysplasia? Mismatch between patient preferences and physician recommendations.

PubMed

Siegel, Corey A; Schwartz, Lisa M; Woloshin, Steven; Cole, Elisabeth B; Rubin, David T; Vay, Tegan; Baars, Judith; Sands, Bruce E

2010-10-01

If dysplasia is found on biopsies during surveillance colonoscopy for ulcerative colitis (UC), many experts recommend colectomy given the substantial risk of synchronous colon cancer. The objective was to learn if UC patients' perceptions of their colon cancer risk and if their preferences for elective colectomy match with physicians' recommendations if dysplasia was found. A self-administered written survey included 199 patients with UC for at least 8 years (mean age 49 years, 52% female) who were recruited from Dartmouth-Hitchcock (n = 104) and the University of Chicago (n = 95). The main outcome was the proportion of patients who disagree with physicians' recommendations for colectomy because of dysplasia. Almost all respondents recognized that UC raised their chance of getting colon cancer. In all, 74% thought it was "unlikely" or "very unlikely" to get colon cancer within the next 10 years and they quantified this risk to be 23%; 60% of patients would refuse a physician's recommendation for elective colectomy if dysplasia was detected, despite being told that they had a 20% risk of having cancer now. On average, these patients would only agree to colectomy if their risk of colon cancer "right now" were at least 73%. UC patients recognize their increased risk of colon cancer and undergo frequent surveillance to reduce their risk. Nonetheless, few seem prepared to follow standard recommendations for elective colectomy if dysplasia is found. This may reflect the belief that surveillance alone is sufficient to reduce their colon cancer risk or genuine disagreement about when it is worth undergoing colectomy.

3g mesalazine granules are superior to 9mg budesonide for achieving remission in active ulcerative colitis: a double-blind, double-dummy, randomised trial.

PubMed

Gross, Volker; Bunganic, Ivan; Belousova, Elena A; Mikhailova, Tatyana L; Kupcinskas, Limas; Kiudelis, Gediminas; Tulassay, Zsolt; Gabalec, Libor; Dorofeyev, Andrey E; Derova, Jelena; Dilger, Karin; Greinwald, Roland; Mueller, Ralph

2011-04-01

Budesonide may be an effective therapy for mild-to-moderately active ulcerative colitis (UC). This study aimed to demonstrate non-inferiority for oral 9mg budesonide once daily (OD) versus 3g mesalazine granules OD. This was an eight-week randomised, double-blind, double-dummy, multicentre study in which patients with mild-to-moderately active UC, defined as Clinical Activity Index (CAI) ≥6 and Endoscopic Index (EI) ≥4, received budesonide (Budenofalk® 3mg capsules×3) or mesalazine (Salofalk® 1000mg granules×3). The primary endpoint was clinical remission at week 8 (CAI ≤4 with stool frequency and rectal bleeding subscores of "0"). 343 patients were randomised (177 budesonide, 166 mesalazine). Fewer patients achieved the primary endpoint with budesonide versus mesalazine (70/177 [39.5%] versus 91/166 [54.8%]) with a difference in proportions of -15.3% (95% CI [-25.7%, -4.8%]; p=0.520 for non-inferiority). The median time to first resolution of symptoms was 14.0 days (budesonide) and 11.0 days (mesalazine) (hazard ratio 1.19; 95% CI [0.94, 1.51]). Mucosal healing was observed in 54/177 (30.5%) budesonide patients versus 65/166 (39.2%) mesalazine patients, a difference of -8.6% (95% CI [-18.7%, 1.4%]; p=0.093). The incidences of adverse events (budesonide 26.6%, mesalazine 25.3%) and serious adverse events (budesonide 1.7%, mesalazine 1.2%) were similar. Once-daily 3g mesalazine administered as granules is superior to 9mg budesonide OD administered as capsules for achieving remission in mild-to-moderately active UC. However, it is noteworthy that remission of UC was attained in about 40% of budesonide-treated patients with a rapid onset of resolution. Copyright © 2010. Published by Elsevier B.V.

Association of extraintestinal manifestations and anaemia with disease outcomes in patients with inflammatory bowel disease.

PubMed

Vegh, Zsuzsanna; Kurti, Zsuzsanna; Gonczi, Lorant; Golovics, Petra Anna; Lovasz, Barbara Dorottya; Szita, Istvan; Balogh, Mihaly; Pandur, Tunde; Vavricka, Stephan R; Rogler, Gerhard; Lakatos, Laszlo; Lakatos, Peter Laszlo

2016-07-01

The association between extraintestinal manifestations (EIMs) and disease activity suggest a common pathogenetic link with inflammatory bowel disease (IBD). We report on the association of EIMs and anaemia with long-term disease outcomes, including treatment steps, hospitalization, and surgery in the prospective population-based IBD inception cohort from Veszprem province. Data of 678 incident IBD patients (Crohn's disease/ulcerative colitis(CD/UC): 331/347) diagnosed from 1st January 2000 to 31st December 2012 were analyzed (CD: m/f: 176/155, median age at diagnosis: 28, IQR: 21-40 years, disease duration: 6, IQR: 2-9 years; UC: m/f: 200/147, median age at diagnosis: 36, IQR: 26-50 years, duration: 7, IQR: 4-10 years). EIMs were present in 30% of the CD and 17.3% of the UC patients. In CD, female gender (p = 0.02) need for steroid (p  < 0.001) and azathioprine (AZA) (p = 0.02), while in UC, young age at onset (p = 0.03), extensive disease (p = 0.003), female gender (p = 0.07), need for steroids (p < 0.001) and AZA (p = 0.004) and need for IBD-related hospitalization (p = 0.01) were associated with the presence of EIMs. Anaemia was present in 56.7% of the CD and 30.2% of the UC patients. In both CD and UC anaemia was associated with age at onset (pCD = 0.001, pUC = 0.04), disease location/extent (pCD = 0.02, pUC < 0.001), steroid and AZA use (for both pCD,UC < 0.001), need for surgery/colectomy (pCD < 0.001, pUC = 0.002) and hospitalization (pCD = 0.004, pUC < 0.001) and in CD, it was associated with anti TNF therapy(p = 0.002). The presence of EIMs was associated with disease phenotype in UC and with treatment strategy in both CD and UC. Additionally, anaemia was associated with hospitalization and surgery in both CD and UC, suggesting that EIMs and anaemia may be helpful in stratifying disease severity in IBD.

The role of unstable NH3 in the formation of nitrogen-rich alpha-U2N(3+x) by the reaction of UC or U with NH3

NASA Astrophysics Data System (ADS)

Katsura, Masahiro; Hirota, Masayuki; Miyake, Masanobu

1994-10-01

Reactions of U or UC with a stream of NH3 or N2 were carried out at 600 and 900 C. It has been found that in high temperature reactions of U or UC with flowing NH3, the catalytic decomposition of NH3 proceeds in parallel with the nitridation reaction of U or UC by action of NH3, which leads to the formation alpha-U2N(3+x), and eventually a steady state is established where the partial pressures of NH3, H2 and N2 (PNH3, PH2, and PN2) in the flowing gas and the N:U ratio of alpha-U2N(3+x) are all uniquely determined. The nitrogen activity a(sub N) of the flowing gas may be increased by suppressing the decomposition of NH3 into H2 and N2. The N:U ratio of alpha-U2N(3+x) increases as the extent of dissociation of NH3, alpha, decreases.

Anaemia in Patients with Inflammatory Bowel Disease - A Nationwide Cross-Sectional Study.

PubMed

Portela, Francisco; Lago, Paula; Cotter, José; Gonçalves, Raquel; Vasconcelos, Helena; Ministro, Paula; Lopes, Susana; Eusébio, Marta; Morna, Henrique; Cravo, Marilia; Peixe, Paula; Cremmers, Isabel; Sousa, Helena; Deus, João; Duarte, Maria; Magro, Fernando

2016-01-01

Anaemia is the most common complication in patients with inflammatory bowel disease (IBD). This study aims to assess the prevalence of anaemia in IBD patients and to know its characteristics with regard to the main IBD clinical features. An observational cross-sectional multicentre study was conducted. We included all patients who had an appointment at the 15 participating centres during the period of 1 month, and who met the following selection criteria: age ≥18, diagnosis of IBD. Disease activity was evaluated by Harvey-Bradshaw Index (HBI) for Crohn's disease (CD), and by Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis (UC). One thousand three hundred and thirteen patients, were included: 54.8% female, mean age 42.8 (interquartile range (25th-75th): 31-53 years), 59% had a diagnosis of CD, 39% of UC and 2% IBD unclassified. The median follow-up since diagnosis was 7 years. The ongoing treatment was aminosalicylates (63.1%), corticosteroids (11.6%), immunomodulators (36.4%) and anti-tumour necrosis factor (27.3%). Anaemia was identified in 244 patients, representing a prevalence of 18.6% (95% CI 16.6-20.9). A majority of cases (90%) have mild/moderate anaemia (mean haemoglobin 11.3 ± 0.8 g/dl). Anaemia was significantly higher in females (p = 0.006), but there were no differences between CDs (19.1%) and UCs (17.7%; p = 0.688). Anaemia was more frequent in patients with active disease (HBI >4; SCCAI >2) than in those in clinical remission (33.6 vs. 15.6%, p < 0.001) and in patients on steroids (36.8%) vs. other treatments (p < 0.001). Only 47% of patients with anaemia were under any specific treatment (oral iron 67%; intravenous iron 41%). Anaemia was more frequent in patients with active disease and in those on corticosteroids. The treatment of anaemia still seems undervalued, whereas more than half of anaemic patients were not receiving any specific treatment and the use of oral iron prevails contrarily to current recommendations. �

Patient satisfaction with different interpreting methods: a randomized controlled trial.

PubMed

Gany, Francesca; Leng, Jennifer; Shapiro, Ephraim; Abramson, David; Motola, Ivette; Shield, David C; Changrani, Jyotsna

2007-11-01

Growth of the foreign-born population in the U.S. has led to increasing numbers of limited-English-proficient (LEP) patients. Innovative medical interpreting strategies, including remote simultaneous medical interpreting (RSMI), have arisen to address the language barrier. This study evaluates the impact of interpreting method on patient satisfaction. 1,276 English-, Spanish-, Mandarin-, and Cantonese-speaking patients attending the primary care clinic and emergency department of a large New York City municipal hospital were screened for enrollment in a randomized controlled trial. Language-discordant patients were randomized to RSMI or usual and customary (U&C) interpreting. Patients with language-concordant providers received usual care. Demographic and patient satisfaction questionnaires were administered to all participants. 541 patients were language-concordant with their providers and not randomized; 371 were randomized to RSMI, 167 of whom were exposed to RSMI; and 364 were randomized to U&C, 198 of whom were exposed to U&C. Patients randomized to RSMI were more likely than those with U&C to think doctors treated them with respect (RSMI 71%, U&C 64%, p < 0.05), but they did not differ in other measures of physician communication/care. In a linear regression analysis, exposure to RSMI was significantly associated with an increase in overall satisfaction with physician communication/care (beta 0.10, 95% CI 0.02-0.18, scale 0-1.0). Patients randomized to RSMI were more likely to think the interpreting method protected their privacy (RSMI 51%, U&C 38%, p < 0.05). Patients randomized to either arm of interpretation reported less comprehension and satisfaction than patients in language-concordant encounters. While not a substitute for language-concordant providers, RSMI can improve patient satisfaction and privacy among LEP patients. Implementing RSMI should be considered an important component of a multipronged approach to addressing language barriers in health

Predictors of Abdominal Pain in Depressed Pediatric Inflammatory Bowel Disease Patients

PubMed Central

Srinath, Arvind I.; Goyal, Alka; Zimmerman, Lori A.; Newara, Melissa C.; Kirshner, Margaret A.; McCarthy, F. Nicole; Keljo, David; Binion, David; Bousvaros, Athos; DeMaso, David R.; Youk, Ada; Szigethy, Eva M.

2015-01-01

Background Pediatric patients with inflammatory bowel disease (IBD) have high rates of abdominal pain. The study aims were to (1) Evaluate biological and psychological correlates of abdominal pain in depressed youth with IBD, (2) Determine predictors of abdominal pain in Crohn’s disease (CD) and ulcerative colitis (UC). Methods 765 patients ages 9–17 with IBD seen over 3 years at two sites were screened for depression. Depressed youth completed comprehensive assessments for abdominal pain, psychological (depression and anxiety), and biological (IBD-related, through disease activity indices and laboratory values) realms. Results 217 patients with IBD (161 CD, 56 UC) were depressed. 163 (120 CD, 43 UC) patients had complete API scores. In CD, abdominal pain was associated with depression (r=0.33; p<0.001), diarrhea (r=0.34; p=0.001), ESR (r=0.22; p=0.02), low albumin (r=0.24; p=.01), weight loss (r=0.33; p=0.001), and abdominal tenderness (r=0.38, p=0.002). A multivariate model with these significant correlates represented 32% of the variance in pain. Only depression (p=0.03), weight loss (p=0.04), and abdominal tenderness (p=0.01) predicted pain for CD patients. In UC, pain was associated with depression (r=0.46; p=0.002) and nocturnal stools (r=.32; p=.046). In the multivariate model with these significant correlates 23% of the variance was explained, and only depression (p=0.02) predicted pain. Conclusions The psychological state of pediatric patients with IBD may increase the sensitivity to abdominal pain. Thus, screening for and treating comorbid depression may prevent excessive medical testing and unnecessary escalation of IBD medications. PMID:24983975

What Was It like? Being in the Pioneer Class at UC Merced

ERIC Educational Resources Information Center

Perry, Lisa

2007-01-01

Entering the UC Merced campus and turning onto Scholars Lane, students saw, in this order, large cow pastures surrounding the campus, tall chainlink fences enclosing construction materials, orange fences stating "limits of construction," and across the small road, the residence facilities. Students who were willing to brave this…

46 CFR 54.25-8 - Radiography (modifies UW-11(a), UCS-57, UNF-57, UHA-33, and UHT-57).

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Radiography (modifies UW-11(a), UCS-57, UNF-57, UHA-33, and UHT-57). 54.25-8 Section 54.25-8 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-8 Radiography (modifies UW-11(a), UCS-57, UNF...

46 CFR 54.25-8 - Radiography (modifies UW-11(a), UCS-57, UNF-57, UHA-33, and UHT-57).

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Radiography (modifies UW-11(a), UCS-57, UNF-57, UHA-33, and UHT-57). 54.25-8 Section 54.25-8 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-8 Radiography (modifies UW-11(a), UCS-57, UNF...

46 CFR 54.25-8 - Radiography (modifies UW-11(a), UCS-57, UNF-57, UHA-33, and UHT-57).

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Radiography (modifies UW-11(a), UCS-57, UNF-57, UHA-33, and UHT-57). 54.25-8 Section 54.25-8 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-8 Radiography (modifies UW-11(a), UCS-57, UNF...

46 CFR 54.25-8 - Radiography (modifies UW-11(a), UCS-57, UNF-57, UHA-33, and UHT-57).

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Radiography (modifies UW-11(a), UCS-57, UNF-57, UHA-33, and UHT-57). 54.25-8 Section 54.25-8 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-8 Radiography (modifies UW-11(a), UCS-57, UNF...

[Infection frequency in patients with chronic idiopathic ulcerative colitis].

PubMed

Yamamoto-Furusho, J K; de León-Rendón, J L; Rodas, L

2012-01-01

Ulcerative Colitis (UC) is a chronic inflammatory bowel disease characterized by diffuse inflammation of the mucosa of the colon. Up to now, diverse observational studies have implicated a wide variety of pathogenic microorganisms as causal and exacerbating factors in UC. Clostridium difficile (C. difficile) infection has been associated with recurrence and treatment failure and its incidence in patients with UC has been on the rise in the last few years. To determine the frequency of infection by different microorganisms in Mexican UC patients. A total of 150 patients with definitive UC diagnosis were studied. All the stool tests for parasites and ova, stool cultures, tests for the C. difficile toxins A and B, and immunohistochemistry for Cytomegalovirus in colon segment biopsies were analyzed. Other demographic and clinical variables of the disease were recorded for their correlation with infection frequency. Infection frequency in UC patients was 28.00%. C. difficile infection was present in 0.013%. Other pathogens were found, such as Endolimax nana (9.00%), Entamoeba histolytica (3.00%), Cytomegalovirus (2.00%), Salmonella (2.00%), Shigella (0.70%), Toxoplasma gondii (0.70%) and Iodamoeba bütschlii (0.70%). Infection frequency was 28.00% in our study and C. difficile infection represented only 0.013%. Copyright © 2012 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

Altered Th1/Th2 cytokine profiles in the intestinal mucosa of patients with inflammatory bowel disease as assessed by quantitative reversed transcribed polymerase chain reaction (RT-PCR).

PubMed Central

Niessner, M; Volk, B A

1995-01-01

Cytokines serve a central function as key factors in the regulation of the intestinal immune response and mediation of tissue damage in inflammatory bowel disease (IBD). Abnormalities in the expression of immunoregulatory cytokines such as IL-2, IL-4, IL-10 and interferon-gamma (IFN-gamma) may indicate a dysregulation of intestinal immunity probably associated with pathogenic events. Therefore, cytokine mRNA concentrations were determined in the mucosa of patients with IBD at sites of active (n = 13) and inactive (n = 12) ulcerative colitis (UC), active (n = 11) and inactive (n = 11) Crohn's disease (CD) and in control patients (n = 14) using quantitative RT-PCR. IL-10 mRNA concentrations were significantly increased in patients with both active UC (P < 0.001) and active CD (P < 0.005) compared with control patients. IFN-gamma mRNA concentrations were also significantly increased both in patients with active UC (P < 0.02) and active CD (P < 0.05) compared with control patients, whereas IL-2 mRNA levels were significantly (P < 0.02) increased only in active CD. IL-4 mRNA expression in the intestinal mucosa was frequently below the detection limit. Our results demonstrate that chronic intestinal inflammation in patients with CD is characterized by an increase of Th1-like cytokines. Furthermore, the increased IL-10 mRNA expression at sites of active IBD suggests that IL-10 is an important regulatory component involved in the control of the inflammatory response in inflammatory bowel disease. Images Fig. 1 Fig. 4 PMID:7664489

p53 expression in patients with ulcerative colitis - associated with dysplasia and carcinoma: a systematic meta-analysis.

PubMed

Lu, Xiaohong; Yu, Yuanjie; Tan, Shiyun

2017-10-25

Tumor suppressor gene p53 expression has been reported in patients with ulcerative colitis (UC). However, the correlation between p53 expression and UC remains controversial. The aim of this meta-analysis was to investigate the association between p53 expression and different pathological types of UC. Publications were searched in the PubMed, Embase, EBSCO, Wangfang, and CNKI databases. The overall odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were summarized in this study. Final 19 papers were identified in this meta-analysis, including 1068 patients with UC and 130 normal tissue samples. Immunohistochemical p53 expression was significantly higher in UC without dysplasia and carcinoma (UC group) compared to normal tissue samples (OR = 3.14, P = 0.001), higher in UC with dysplasia than in UC group (OR = 10.76, P < 0.001), and higher in UC with colorectal cancer (CRC) than in UC with dysplasia (OR = 1.69, P = 0.035). Subgroup analysis of ethnicity (UC group vs. normal tissues) showed that p53 expression was correlated with UC in Asians, but not in Caucasians. When UC with dysplasia was compared to UC group, p53 expression was linked to UC with dysplasia among both Asians and Caucasians. When UC-CRC was compared to UC with dysplasia, p53 expression was not associated with UC-CRC in both Caucasians and Asians. p53 expression was closely associated with UC-CRC development. p53 expression showed different ethnic characteristics among different pathological types of UC.

Thiopurine Therapy Reduces the Incidence of Colorectal Neoplasia in Patients with Ulcerative Colitis. Data from the ENEIDA Registry.

PubMed

Gordillo, Jordi; Cabré, Eduard; Garcia-Planella, Esther; Ricart, Elena; Ber-Nieto, Yolanda; Márquez, Lucía; Rodríguez-Moranta, Francisco; Ponferrada, Ángel; Vera, Isabel; Gisbert, Javier P; Barrio, Jesús; Esteve, Maria; Merino, Olga; Muñoz, Fernando; Domènech, Eugeni

2015-12-01

Patients with ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC), but recent studies suggest a lower risk than previously reported. The aim was to evaluate the incidence of dysplasia, CRC and related risk factors in UC patients from a Spanish nationwide database. All UC patients were identified and retrospectively reviewed. Clinical-epidemiological data and the finding of dysplasia and/or CRC were collected. A total of 831 UC patients were included. Twenty-six cases of CRC in 26 patients and 29 cases of high-grade dysplasia (HGD) in 24 patients were found, accounting for 55 diagnoses of advanced neoplasia (AN = CRC and/or HGD) in 45 patients (33% of them within the first 8 years after UC diagnosis). The cumulative risk of AN was 2, 5.3 and 14.7% at 10, 20 and 30 years, respectively. Concomitant primary sclerosing cholangitis (odds ratio [OR] 10.90; 95% confidence interval [CI] 3.75-31.76, p < 0.001), extensive UC (OR 2.10, 95% CI 1.01-4.38, p = 0.048), UC diagnosis at an older age (OR 2.23, 95% CI 1.03-4.83, p = 0.043) and appendectomy prior to UC diagnosis (OR 2.66, 95% CI 1.06-6.71, p = 0.038) were independent risk factors for AN. Use of thiopurines (OR 0.21, 95% CI 0.06-0.74, p = 0.015) and being in a surveillance colonoscopy programme (OR 0.33; 95% CI 0.16-0.67; p = 0.002) were independent protective factors for AN. The risk of AN among UC patients is lower than previously reported but steadily increases from the time of UC diagnosis. The widespread use of thiopurines may have influenced this reduced incidence of UC-related neoplasias. 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.

Once-daily versus multiple-daily mesalamine for patients with ulcerative colitis: a meta-analysis.

PubMed

Tong, Jin Lu; Huang, Mei Lan; Xu, Xi Tao; Qiao, Yu Qi; Ran, Zhi Hua

2012-04-01

To systematically review the efficacy and safety of once-daily (OD) mesalamine for the treatment of ulcerative colitis (UC) compared with multiple-daily (MD) mesalamine. Electronic databases up to July 2011 were searched for related studies evaluating the efficacy of OD vs MD for treatment of UC. Only randomized controlled trials (RCTs) were considered eligible. Remission rates or relapse rates were analyzed using intention-to-treat (ITT) and per-protocol (PP) analysis. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated. Publication bias was assessed with a funnel plot. Overall 10 RCTs including 9 full-text manuscripts and one abstract met the inclusion criteria. OD dosing of mesalamine was shown to be as effective as MD dosing for the maintenance of clinical remission in patients with quiescent UC (RR = 1.00, 95% CI 0.89-1.12) by ITT analysis. For active UC, a mild but significant benefit was achieved by OD dosing compared with MD dosing (RR = 0.80, 95% CI 0.64-0.99). Total adverse events were similar using OD and MD mesalamine in quiescent UC (RR = 1.06, 95% CI 0.93-1.20). Compliance with OD was slightly better than with MD (RR = 0.92, 95% CI 0.82-1.03). OD mesalamine is as effective and has a comparable safety profile as MD regimens for the maintenance treatment of UC, and is even more effective for inducing remission in active UC. © 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

Rapid response to vedolizumab therapy in biologic-naïve patients with inflammatory bowel diseases.

PubMed

Feagan, Brian G; Lasch, Karen; Lissoos, Trevor; Cao, Charlie; Wojtowicz, Abigail M; Khalid, Javaria Mona; Colombel, Jean-Frédéric

2018-05-29

Vedolizumab, a humanized monoclonal antibody against α4β7 integrin, is used to treat adults with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). We investigated the time course of clinical response to vedolizumab in patients who were and were not previously treated with tumor necrosis factor (TNF) antagonists. We performed a post-hoc analysis of data from phase 3, randomized, controlled trials of vedolizumab vs placebo in adult patients with UC (n=374) or CD (n=784). We collected data on patient-reported symptoms (rectal bleeding and stool frequency for patients with UC, abdominal pain and loose stool frequency for patients with CD) reported at weeks 2, 4, and 6 of treatment. We reported mean percentage score changes from baseline and proportions of patients who achieved predefined scores. We performed multivariate logistic regression analysis to identify factors associated with an early response (at week 2). In patients with UC (overall or naïve to TNF antagonist therapy), a significantly greater percentage of patients given vedolizumab achieved the predefined composite symptom score at weeks 2, 4, and 6 compared to those given placebo. In patients with CD who were naïve to TNF antagonists, a significantly greater percentage of patients given vedolizumab achieved the predefined score at weeks 2 and 4 compared to those given placebo. Among patients with UC given vedolizumab, 19.1% (overall) and 22.3% (TNF antagonist naïve) achieved a composite score of rectal bleeding of 0 and stool frequency ≤1 at week 2 compared to 10% (overall) and 6.6% (TNF antagonist naïve) of those receiving placebo. Among TNF antagonist-naïve patients with CD, 15.0% of those given vedolizumab achieved an average daily composite score of abdominal pain ≤1 and loose stool frequency ≤3 at week 2 (compared to 7.9% given placebo), and 23.8% of those given vedolizumab achieved these by week 4 (compared to 10.3% given placebo). In a post-hoc analysis of

Total Ionizing Dose Test Report for the UC1823A Pulse Width Modulator

NASA Technical Reports Server (NTRS)

Chen, Dakai; Forney, James

2017-01-01

The purpose of this study is to examine the total ionizing dose susceptibility for the UC1823A pulse width modulator manufactured by Texas Instruments, Inc. The part is suspected to be vulnerable to enhanced low dose rate sensitivity (ELDRS).

Cost-Utility Analysis of Pharmaceutical Care Intervention Versus Usual Care in Management of Nigerian Patients with Type 2 Diabetes.

PubMed

Adibe, Maxwell O; Aguwa, Cletus N; Ukwe, Chinwe V

To assess the cost-effectiveness of pharmaceutical care (PC) intervention versus usual care (UC) in the management of type 2 diabetes. This study was a randomized, controlled study with a 12-month patient follow-up in two Nigerian tertiary hospitals. One hundred and ten patients were randomly assigned to each of the "intervention" (PC) and the "control" (UC) groups. Patients in the UC group received the usual/conventional care offered by the hospitals. Patients in the PC group received UC and PC in the form of structural self-care education and training for 12 months. The economic evaluation was based on patients' perspective. Costs of management of individual complications were calculated from activities involved in their management by using activity-based costing. The impact of the interventions on quality of life was estimated by using the HUI23S4EN.40Q (Mark index 3) questionnaire. The primary outcomes were incremental cost-utility ratio and net monetary benefit. An intention-to-treat approach was used. Two-sample comparisons were made by using Student's t tests for normally distributed variables data at baseline, 6 months, and 12 months. Comparisons of proportions were done by using the chi-square test. The PC intervention led to incremental cost and effect of Nigerian naira (NGN) 10,623 ($69) and 0.12 quality-adjusted life-year (QALY) gained, respectively, with an associated incremental cost-utility ratio of NGN 88,525 ($571) per QALY gained. In the cost-effectiveness acceptability curve, the probability that PC was more cost-effective than UC was 95% at the NGN 250,000 ($1613) per QALY gained threshold and 52% at the NGN 88,600 ($572) per QALY gained threshold. The PC intervention was very cost-effective among patients with type 2 diabetes at the NGN 88,525 ($571.13) per QALY gained threshold, although considerable uncertainty surrounds these estimates. Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by

Increased Enterococcus faecalis infection is associated with clinically active Crohn disease

PubMed Central

Zhou, Youlian; Chen, Huiting; He, Hanchang; Du, Yanlei; Hu, Jiaqi; Li, Yingfei; Li, Yuyuan; Zhou, Yongjian; Wang, Hong; Chen, Ye; Nie, Yuqiang

2016-01-01

Abstract This study was performed to investigate the relationship between the abundance of pathogenic gut microbes in Chinese patients with inflammatory bowel disease (IBD) and disease severity. We collected clinical data and fecal samples from 47 therapy-naive Chinese patients with ulcerative colitis (UC), 67 patients with Crohn disease (CD), and 48 healthy volunteers. Bacteria levels of Fusobacterium species (spp), enterotoxigenic Bacteroides fragilis (B fragilis), enteropathogenic Escherichia coli (E coli), and Enterococcus faecalis (E faecalis) were assessed by quantitative real-time PCR (qRT-PCR). Spearman correlation coefficients were calculated to test associations between bacterial content and clinical parameters. Compared to healthy controls, the levels of both Fusobacterium spp and E faecalis were significantly increased in the feces of patients with IBD (P < 0.01). B fragilis levels were higher (P < 0.05) and E faecalis levels lower (P < 0.05) in patients with CD compared to those with UC. Increased E faecalis colonization in CD associated positively with disease activity (P = 0.015), Crohn disease activity index (CDAI; R = 0.3118, P = 0.0108), and fecal calprotectin (P = 0.016). E faecalis and Fusobacterium spp are significantly enriched in patients with IBD, and increased E faecalis infection is associated with clinically active CD. PMID:27684872

Increased Enterococcus faecalis infection is associated with clinically active Crohn disease.

PubMed

Zhou, Youlian; Chen, Huiting; He, Hanchang; Du, Yanlei; Hu, Jiaqi; Li, Yingfei; Li, Yuyuan; Zhou, Yongjian; Wang, Hong; Chen, Ye; Nie, Yuqiang

2016-09-01

This study was performed to investigate the relationship between the abundance of pathogenic gut microbes in Chinese patients with inflammatory bowel disease (IBD) and disease severity.We collected clinical data and fecal samples from 47 therapy-naive Chinese patients with ulcerative colitis (UC), 67 patients with Crohn disease (CD), and 48 healthy volunteers. Bacteria levels of Fusobacterium species (spp), enterotoxigenic Bacteroides fragilis (B fragilis), enteropathogenic Escherichia coli (E coli), and Enterococcus faecalis (E faecalis) were assessed by quantitative real-time PCR (qRT-PCR). Spearman correlation coefficients were calculated to test associations between bacterial content and clinical parameters.Compared to healthy controls, the levels of both Fusobacterium spp and E faecalis were significantly increased in the feces of patients with IBD (P < 0.01). B fragilis levels were higher (P < 0.05) and E faecalis levels lower (P < 0.05) in patients with CD compared to those with UC. Increased E faecalis colonization in CD associated positively with disease activity (P = 0.015), Crohn disease activity index (CDAI; R = 0.3118, P = 0.0108), and fecal calprotectin (P = 0.016).E faecalis and Fusobacterium spp are significantly enriched in patients with IBD, and increased E faecalis infection is associated with clinically active CD.

The risk of bladder cancer in patients with urinary calculi: a meta-analysis.

PubMed

Yu, Zhang; Yue, Wu; Jiuzhi, Li; Youtao, Jiang; Guofei, Zhang; Wenbin, Guo

2018-01-05

The objective of this meta-analysis was to evaluate the association between a history of urinary calculi (UC) and the risk of bladder cancer (BC). A literature search was performed from inception until July 2017. Studies that reported odds ratios (OR), relative risks or hazard ratios comparing the risk of BC in patients with the history of UC vs those without the history of UC were included. Pooled odds ratios and 95% confidence interval (CI) were calculated using a random-effect or fixed-effect method. Thirteen studies were included in our analysis to assess the association between a history of UC and risk of BC. The pooled OR of BC in patients with UC was 1.87 (95% CI, 1.45-2.41). Bladder calculi [OR, 2.17 (95% CI, 1.52-3.08)] had a higher risk of BC than kidney calculi [OR, 1.39 (95% CI, 1.06-1.82)]. The subjects had a history of UC that was associated with increased BC risk both in males [OR, 2.04 (95% CI, 1.41-2.96)] and in females [OR, 2.99 (95% CI, 2.37-3.76)]. The subgroup analysis demonstrated that UC increasing risk of BC both in case-control studies [OR, 1.75 (95% CI, 1.25-2.45)] and cohort studies [OR, 2.27 (95% CI, 1.55-3.32)]. The pooled OR of BC risk in patients with UC were 1.60 (95% CI, 1.15-2.24) in America, 1.36 (95% CI, 1.14-1.64) in Europe and 3.05 (95% CI, 2.21-4.21) in Asia, respectively. Our study demonstrates a significant increased risk of BC in patients with prior UC. This finding suggests that a history of UC is associated with BC and may impact clinical management and cancer surveillance. Further studies still needed to confirm the findings.

Assessment of selected psychological factors in patients with inflammatory bowel disease

PubMed Central

Kaczówka, Anna; Jeżewska, Maria

2015-01-01

Introduction In the majority of patients with inflammatory bowel diseases (IBD) mental health problems are demonstrated in the form of excessive anxiety and unstable emotional reactions. Emotional instability affects the wellbeing of these patients, and also their attitude towards the disease and the course of treatment. Aim The objective of the study is to evaluate psychological factors in patients with IBD, and to compare patients with ulcerative colitis (UC) and patients suffering from Crohn's disease (CD) with respect to intensity of these factors. Material and methods The study included 108 patients with IBD. NEO-FFI and type-D Scale were used to evaluate personality traits. Anxiety level was measured with STAI. CECS was used to measure the patients’ tendency to suppress negative emotions. Results In the patients with CD 45% of subjects presented type D personality. In the group of patients with UC, type D personality was found in 38%. The higher levels of neuroticism and extraversion were observed in patients with UC, whereas the patients with CD exhibited a higher level of openness to experience and agreeableness. In patients with CD the levels of state anxiety were elevated, whereas in patients with UC higher scores were both for state and trait anxiety. Conclusions There were no statistically significant differences in terms of personality factors in a group of patients with CD and UC. It was found that the majority of patients with IBD suffer elevated or high sense of anxiety. PMID:27110311

Delayed-release oral mesalamine 4.8 g/day (800 mg tablets) compared with 2.4 g/day (400 mg tablets) for the treatment of mildly to moderately active ulcerative colitis: The ASCEND I trial

PubMed Central

Hanauer, Stephen B; Sandborn, William J; Dallaire, Christian; Archambault, André; Yacyshyn, Bruce; Yeh, Chyon; Smith-Hall, Nancy

2007-01-01

BACKGROUND: Delayed-release oral mesalamine 2.4 g/day to 4.8 g/day has been shown to be effective in treating mildly to moderately active ulcerative colitis (UC), but it is unknown whether an initial dose of 4.8 g/day is more effective than 2.4 g/day in patients with mildly to moderately active UC and in the subgroup with moderate disease. PATIENTS AND METHODS: A six-week, multicentre, randomized, double-blind, controlled trial assessing the safety and clinical efficacy of a new dose (ASCEND I) of medication randomly assigned 301 adults with mildly to moderately active UC to delayed-release oral mesalamine 2.4 g/day (400 mg tablet [n=154]) or 4.8 g/day (800 mg tablet [n=147]). The primary efficacy end point was overall improvement (ie, treatment success), defined as complete remission or response to therapy from baseline to week 6. Primary safety end points were adverse events and laboratory evaluations. Data were also analyzed separately for the prespecified subgroup of patients with moderate UC at baseline. RESULTS: Treatment success was not statistically different between the treatment groups at week 6; 51% of the group (77 of 150) who received delayed-release oral mesalamine 2.4 g/day and 56% of the group (76 of 136) who received 4.8 g/day reached the efficacy end point (P=0.441). Among the moderate disease subgroup, however, the higher initial dose was more effective; 57% of patients (53 of 93) given delayed-release oral mesalamine 2.4 g/day and 72% of patients (55 of 76) given 4.8 g/day achieved treatment success (P=0.0384). Both regimens were well tolerated. CONCLUSIONS: Delayed-release oral mesalamine is an effective and well-tolerated initial therapy in patients with mildly to moderately active UC, and a 4.8 g/day dose may enhance treatment success rates in patients with moderate disease compared with mesalamine 2.4 g/day. PMID:18080055

Mesalamine dose escalation reduces fecal calprotectin in patients with quiescent ulcerative colitis.

PubMed

Osterman, Mark T; Aberra, Faten N; Cross, Raymond; Liakos, Steven; McCabe, Robert; Shafran, Ira; Wolf, Douglas; Hardi, Robert; Nessel, Lisa; Brensinger, Colleen; Gilroy, Erin; Lewis, James D

2014-11-01

Among patients with quiescent ulcerative colitis (UC), lower fecal concentrations of calprotectin are associated with lower rates of relapse. We performed an open-label, randomized controlled trial to investigate whether increasing doses of mesalamine reduce concentrations of fecal calprotectin (FC) in patients with quiescent UC. We screened 119 patients with UC in remission on the basis of Simple Clinical Colitis Activity Index scores, FC >50 μg/g, and intake of no more than 3 g/day mesalamine. Participants taking mesalamine formulations other than multimatrix mesalamine were switched to multimatrix mesalamine (2.4 g/day) for 6 weeks; 52 participants were then randomly assigned (1:1) to a group that continued its current dose of mesalamine (controls, n = 26) or a group that increased its dose by 2.4 g/day for 6 weeks (n = 26). The primary outcome was continued remission with FC <50 μg/g. Secondary outcomes were continued remission with FC <100 μg/g or <200 μg/g (among patients with pre-randomization values above these levels). The primary outcome was achieved by 3.8% of controls and 26.9% of the dose escalation group (P = .0496). More patients in the dose escalation group reduced FC to below 100 μg/g (P = .04) and 200 μg/g (P = .005). Among the patients who were still in remission after the randomization phase, clinical relapse occurred sooner in patients with FC >200 μg/g compared with those with FC <200 μg/g (P = .01). Among patients with quiescent UC and increased levels of FC, increasing the dose of mesalamine by 2.4 g/day reduced fecal concentrations of calprotectin to those associated with lower rates of relapse. Clinicaltrials.gov number: NCT00652145. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Mesalamine Dose Escalation Reduces Fecal Calprotectin In Patients With Quiescent Ulcerative Colitis

PubMed Central

Osterman, Mark T.; Aberra, Faten N; Cross, Raymond; Liakos, Steven; McCabe, Robert; Shafran, Ira; Wolf, Douglas; Hardi, Robert; Nessel, Lisa; Brensinger, Colleen; Gilroy, Erin; Lewis, James D.

2014-01-01

Background & Aims Among patients with quiescent ulcerative colitis (UC), lower fecal concentrations of calprotectin are associated with lower rates of relapse. We performed an open-label, randomized, controlled trial to investigate whether increasing doses mesalamine reduce concentrations of fecal calprotectin (FC) in patients with quiescent UC. Methods We screened 119 patients with UC in remission, based on Simple Clinical Colitis Activity Index scores, FC >50 mcg/g, and intake of no more than 3g/day of mesalamine. Participants taking mesalamine formulations other than multimatrix mesalamine were switched to multimatrix mesalamine (2.4 g/day) for 6 weeks; 52 participants were then randomly assigned (1:1) to a group that continued its current dose of mesalamine (controls, n=26) or a group that increased its dose by 2.4 g/day for 6 weeks (n=26). The primary outcome was continued remission with FC<50 mcg/g. Secondary outcomes were continued remission with FC<100 mcg/g or <200 mcg/g (among patients with pre-randomization values above these levels). Results The primary outcome was achieved by 3.8% of controls and 26.9% of the dose escalation group (P=.0496). More patients in the dose escalation group reduced FC to below 100 mcg/g (P=.04) and 200 mcg/g (P=.005). Among the patients who were still in remission after the randomization phase, clinical relapse occurred sooner in patients with FC >200 mcg/g compared to those with FC <200 mcg/g (P=.01). Conclusion Among patients with quiescent UC and increased levels of FC, increasing the dose of mesalamine by 2.4 g/day reduced fecal concentrations of calprotectin to those associated with lower rates of relapse. Clinicaltrials.gov: NCT00652145 PMID:24793028

Systematic Review and Meta-analysis: Fecal Microbiota Transplantation for Treatment of Active Ulcerative Colitis.

PubMed

Narula, Neeraj; Kassam, Zain; Yuan, Yuhong; Colombel, Jean-Frederic; Ponsioen, Cyriel; Reinisch, Walter; Moayyedi, Paul

2017-10-01

Changes in the colonic microbiota may play a role in the pathogenesis of ulcerative colitis (UC) and restoration of healthy gut microbiota may ameliorate disease. A systematic review and meta-analysis was conducted to assess fecal microbiota transplantation (FMT) as a treatment for active UC. A literature search was conducted to identify high-quality studies of FMT as a treatment for patients with UC. The primary outcome was combined clinical remission and endoscopic remission or response. Secondary outcomes included clinical remission, endoscopic remission, and serious adverse events. Odds ratios with 95% confidence intervals (CIs) are reported. Overall, 4 studies with 277 participants were eligible for inclusion. Among 4 randomized controlled trials, FMT was associated with higher combined clinical and endoscopic remission compared with placebo (risk ratio UC not in remission was 0.80; 95% CI: 0.71-0.89) with a number needed to treat of 5 (95% CI: 4-10). There was no statistically significant increase in serious adverse events with FMT compared with controls (risk ratio adverse event was 1.4; 95% CI: 0.55-3.58). Among randomized controlled trials, short-term use of FMT shows promise as a treatment to induce remission in active UC based on the efficacy and safety observed. However, there remain many unanswered questions that require further research before FMT can be considered for use in clinical practice.

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.

Exposure-efficacy Relationships for Vedolizumab Induction Therapy in Patients with Ulcerative Colitis or Crohn's Disease.

PubMed

Rosario, Maria; French, Jonathan L; Dirks, Nathanael L; Sankoh, Serap; Parikh, Asit; Yang, Huyuan; Danese, Silvio; Colombel, Jean-Frédéric; Smyth, Michael; Sandborn, William J; Feagan, Brian G; Reinisch, Walter; Sands, Bruce E; Sans, Miguel; Fox, Irving

2017-08-01

A positive relationship between vedolizumab trough serum concentrations and clinical outcomes in patients with ulcerative colitis [UC] or Crohn's disease [CD] has been reported. Here we further explore exposure-efficacy relationships for vedolizumab induction therapy in post hoc analyses of GEMINI study data. Vedolizumab trough concentrations at Week 6 or 10 were grouped in quartiles and clinical outcome rates calculated. Exposure-efficacy relationships at Week 6 and potential baseline covariate effects were explored using logistic regression and individual predicted cumulative average concentration through Week 6 [Caverage] as exposure measure. Higher vedolizumab concentrations were associated with higher clinical remission rates; the exposure-efficacy relationship was steeper for UC than CD. Unadjusted analyses overestimated the relationship, more so for CD. From covariate-adjusted models, average probability of remission at Week 6 increased by approximately 15% for UC and 10% for CD between Caverage values of 35 and 84 µg/ml [5th and 95th percentiles, respectively]. On average, patients with higher albumin, lower faecal calprotectin [UC only], lower C-reactive protein [CD only], and no previous tumour necrosis factor-α [TNFα] antagonist use had a higher remission probability. Previous TNFα antagonist use had the greatest impact; remission probability was approximately 10% higher in treatment-naïve patients. Higher vedolizumab serum concentrations were associated with higher remission rates after induction therapy in patients with moderately to severely active UC or CD. This relationship is affected by several factors, including previous TNFα antagonist use. Prospective studies are needed to assess vedolizumab dose individualisation and optimisation. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Production of UC-labeled gas in BACTEC Neisseria Differentiation kits by Neisseria cinerea

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

Boyce, J.M.; Mitchell, E.B. Jr.; Knapp, J.S.

1985-09-01

Six strains of Neisseria cinerea were tested in BACTEC Neisseria Differentiation kits (Johnston Laboratories, Inc., Towson, Md.), and all yielded positive glucose growth indices and negative maltose and fructose growth indices. These results were similar to those achieved with Neisseria gonorrhoeae. However, most of the N. cinerea isolates tested yielded 3-h glucose growth indices that were lower than those obtained with gonococci. UC-labeled gas was produced significantly faster by N. gonorrhoeae than by N. cinerea. Additional studies suggested that the UC-labeled gas produced by N. cinerea was carbon dioxide. N. cinerea strains were similar to Branhamella catarrhalis strains because bothmore » species failed to produce detectable acid from glucose, maltose, sucrose, fructose, and lactose in cysteine-tryptic agar media. However, in contrast to N. cinerea strains, B. catarrhalis strains did not metabolize glucose in BACTEC Neisseria Differentiation kits.« less

Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation -- a placebo-controlled study.

PubMed

Watanabe, M; Nishino, H; Sameshima, Y; Ota, A; Nakamura, S; Hibi, T

2013-08-01

Mesalazine suppositories are recommended and widely used as the standard therapy in induction and maintenance of remission for proctitis. To evaluate the efficacy of mesalazine suppositories in patients with ulcerative colitis (UC) and rectal inflammation; and in patient groups categorised by the extent of lesions. This study was a phase III multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Mild-to-moderate UC patients with rectal inflammation were randomly assigned either a 1 g mesalazine or placebo suppository. The suppository was administered in the rectum once daily for 4 weeks. The primary efficacy end point was the rate of endoscopic remission (mucosal score of 0 or 1) after 4 weeks. The endoscopic remission rates after 4 weeks in the mesalazine and placebo suppository groups were 81.5% and 29.7%, respectively, and the superiority of mesalazine to placebo was confirmed (P < 0.0001, chi-squared test). For proctitis, the endoscopic remission rates after 4 weeks were 83.8% and 36.1% in the mesalazine and placebo suppository groups, respectively, and the corresponding rates for all other types of UC were 78.6% and 21.4%, respectively. The superiority of mesalazine to placebo was confirmed in both subgroups (P < 0.0001, Fisher's exact test). The percentage of patients without bleeding was significantly higher in the mesalazine group than the placebo group from Day 3 of treatment (P = 0.0001, Fisher's exact test). The effectiveness of mesalazine suppositories in all types of UC patients with rectal inflammation was confirmed for the first time in a double-blind, placebo-controlled, parallel-group study (JapicCTI- 111421). © 2013 John Wiley & Sons Ltd.

You look all right to me: compromised nutritional status in paediatric patients with ulcerative colitis.

PubMed

Hill, Rebecca J; Davies, Peter S W

2013-04-01

It is reported that malnutrition is not a feature of ulcerative colitis (UC). Body mass index (BMI) is frequently used clinically to indicate nutritional status; however, it is a proxy measure at best, and body cell mass (BCM) is a much more accurate representation. The present study aims to investigate BMI in patients with UC in relation to their BCM. A total of 18 patients (7M; 11F) had their nutritional status (BCM) measured using total body potassium⁴⁰ counting every 6 months to yield a total of 77 measurements. BCM measurements were adjusted for height and sex, and BMI was calculated as weight/height², with z scores determined for both parameters. Disease activity was determined using the Pediatric Ulcerative Colitis Activity Index. Mean (±SD) height, weight, BMI, and BCM z scores were 0.39 (0.96), 0.20 (1.08), -0.05 (1.18), and -0.74 (1.41), respectively. No correlation was found between BMI and BCM z scores, and these z scores were significantly different (P=0.02), particularly in the moderate/severe disease activity group (P=0.01). Mean BCM z scores were -0.69 (1.65) of a z score below BMI z scores. Furthermore, where BMI z scores showed no relation to disease activity and no differences between disease activity categories, BCM z scores were significantly negatively correlated (r=-0.32, P=0.01), with significantly lower scores found in the moderate/severe group (P=0.01). Simply calculating BMI in patients with UC does not give adequate information regarding nutritional status, and more accurate, yet easily accessible "bedside" techniques need to be determined to improve patient care.

Inflammatory Bowel Disease Patients' Participation, Attitude and Preferences Toward Exercise.

PubMed

Chae, J; Yang, H I; Kim, B; Park, S J; Jeon, J Y

2016-07-01

The purpose of the study was to investigate the level of exercise participation in patients with inflammatory bowel disease (IBD) and to investigate their intention, attitude and preference toward exercise. The data of 158 IBD patients that participated in a self-administered survey at Severance Hospital between March 2013 and November 2013 were included in this cross sectional and descriptive analysis. Questionnaires included 3 sections to determine the IBD patient's current exercise participation, attitude toward exercise, and exercise preferences. This study investigated IBD patients both collectively, and according to their specific disease: Crohn's disease (CD) (n=62), Ulcerative colitis (UC) (n=73) and intestinal Behçet's disease (BD) (n=23). IBD patients currently participate in 103 min/week of exercise including mild, moderate and strenuous intensity, with BD patients being the least active, followed by CD, and UC being most active. The majority of IBD patients found exercise to be pleasant (57.7%), beneficial (80.5%), sensible (71.8%), uplifting (61%) and good (70.5%), and 44.4% found exercise to be enjoyable. This study shows the IBD patients' participation, attitude and preferences toward exercise and provides much needed information for the development of evidence based exercise programs that are specific to IBD. © Georg Thieme Verlag KG Stuttgart · New York.

Comparison of clinicopathologic characteristics of urothelial carcinoma between patients after renal transplantation and on dialysis.

PubMed

Zhang, Bo; Shen, Cheng; Han, Wen-ke; Yu, Wei

2014-09-15

Urothelial carcinoma (UC) is a common complication after renal replacement therapy (RRT) among Chinese end-stage renal disease (ESRD) patients. It is unclear whether there are any differences in the clinicopathologic characteristics of UC between renal transplantation (RT) and dialysis patients; such differences could impact RRT modality selection. We retrospectively reviewed clinicopathologic data for 27 RT patients and 40 dialysis patients who were diagnosed with UC in our center to explore differences in the clinicopathologic characteristics of UC and prognoses between the two groups. The median follow-up period was 92 months (2-137) for the RT group and 71 months (18-155) for the dialysis group. The demographic and baseline data showed no significant differences between the two groups. Upper urinary tract UC (UUC) occurred more frequently in the RT group (22 UUCs in 39 UCs), whereas bladder UC (BUC) predominated in the dialysis group (33 BUCs in 49 UCs) (P=0.025). The pathologic grading in the RT group was significantly higher than that in the dialysis group (P=0.046 for WHO1973 grading, P=0.026 for WHO2004 grading), whereas the difference in tumor stage was not significant (P=0.089). The RT group manifested a higher recurrence rate than the dialysis group (P=0.024). However, the overall and cancer-specific survival rates between the two groups were not significantly different (P=0.239 and P=0.818, respectively). Certain traits of UC, including tumor site, pathologic grading, and recurrence-free survival, were notably different between RT and dialysis patients, but the overall and cancer-specific survival rates were similar.

Decreased Plasma Histidine Level Predicts Risk of Relapse in Patients with Ulcerative Colitis in Remission

PubMed Central

Hisamatsu, Tadakazu; Ono, Nobukazu; Imaizumi, Akira; Mori, Maiko; Suzuki, Hiroaki; Uo, Michihide; Hashimoto, Masaki; Naganuma, Makoto; Matsuoka, Katsuyoshi; Mizuno, Shinta; Kitazume, Mina T.; Yajima, Tomoharu; Ogata, Haruhiko; Iwao, Yasushi; Hibi, Toshifumi; Kanai, Takanori

2015-01-01

Ulcerative colitis (UC) is characterized by chronic intestinal inflammation. Patients with UC have repeated remission and relapse. Clinical biomarkers that can predict relapse in UC patients in remission have not been identified. To facilitate the prediction of relapse of UC, we investigated the potential of novel multivariate indexes using statistical modeling of plasma free amino acid (PFAA) concentrations. We measured fasting PFAA concentrations in 369 UC patients in clinical remission, and 355 were observed prospectively for up to 1 year. Relapse rate within 1 year was 23% (82 of 355 patients). The age- and gender-adjusted hazard ratio for the lowest quartile compared with the highest quartile of plasma histidine concentration was 2.55 (95% confidence interval: 1.41–4.62; p = 0.0020 (log-rank), p for trend = 0.0005). We demonstrated that plasma amino acid profiles in UC patients in clinical remission can predict the risk of relapse within 1 year. Decreased histidine level in PFAAs was associated with increased risk of relapse. Metabolomics could be promising for the establishment of a non-invasive predictive marker in inflammatory bowel disease. PMID:26474176

Initial source and site characterization studies for the U.C. Santa Barbara campus

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

Archuleta, R.; Nicholson, C.; Steidl, J.

1997-12-01

The University of California Campus-Laboratory Collaboration (CLC) project is an integrated 3 year effort involving Lawrence Livermore National Laboratory (LLNL) and four UC campuses - Los Angeles (UCLA), Riverside (UCR), Santa Barbara (UCSB), and San Diego (UCSD) - plus additional collaborators at San Diego State University (SDSU), at Los Alamos National Laboratory and in industry. The primary purpose of the project is to estimate potential ground motions from large earthquakes and to predict site-specific ground motions for one critical structure on each campus. This project thus combines the disciplines of geology, seismology, geodesy, soil dynamics, and earthquake engineering into amore » fully integrated approach. Once completed, the CLC project will provide a template to evaluate other buildings at each of the four UC campuses, as well as provide a methodology for evaluating seismic hazards at other critical sites in California, including other UC locations at risk from large earthquakes. Another important objective of the CLC project is the education of students and other professional in the application of this integrated, multidisciplinary, state-of-the-art approach to the assessment of earthquake hazard. For each campus targeted by the CLC project, the seismic hazard study will consist of four phases: Phase I - Initial source and site characterization, Phase II - Drilling, logging, seismic monitoring, and laboratory dynamic soil testing, Phase III - Modeling of predicted site-specific earthquake ground motions, and Phase IV - Calculations of 3D building response. This report cover Phase I for the UCSB campus and incudes results up through March 1997.« less

UC Berkeley's Celebration of the International Year of Astronomy 2009

NASA Astrophysics Data System (ADS)

Cobb, B. E.; Croft, S.; Silverman, J. M.; Klein, C.; Modjaz, M.

2010-08-01

We present the astronomy outreach efforts undertaken for the International Year of Astronomy 2009 at the University of California, Berkeley. Our department-wide endeavors included a monthly public lecture series by UC Berkeley astronomers and a major astronomy outreach event during a campus-wide university "open house," which included solar observing and a Starlab Planetarium. In addition to sharing our outreach techniques and outcomes, we discuss some of our unique strategies for advertising our events to the local community.

Evaluation of the Program in Medical Education for the Urban Underserved (PRIME-US) at the UC Berkeley-UCSF Joint Medical Program (JMP): The First 4 Years.

PubMed

Sokal-Gutierrez, Karen; Ivey, Susan L; Garcia, Roxanna M; Azzam, Amin

2015-01-01

Medical educators, clinicians, and health policy experts widely acknowledge the need to increase the diversity of our healthcare workforce and build our capacity to care for medically underserved populations and reduce health disparities. The Program in Medical Education for the Urban Underserved (PRIME-US) is part of a family of programs across the University of California (UC) medical schools aiming to recruit and train physicians to care for underserved populations, expand the healthcare workforce to serve diverse populations, and promote health equity. PRIME-US selects medical students from diverse backgrounds who are committed to caring for underserved populations and provides a 5-year curriculum including a summer orientation, a longitudinal seminar series with community engagement and leadership-development activities, preclerkship clinical immersion in an underserved setting, a master's degree, and a capstone rotation in the final year of medical school. This is a mixed-methods evaluation of the first 4 years of the PRIME-US at the UC Berkeley-UC San Francisco Joint Medical Program (JMP). From 2006 to 2010, focus groups were conducted each year with classes of JMP PRIME-US students, for a total of 11 focus groups; major themes were identified using content analysis. In addition, 4 yearly anonymous, online surveys of all JMP students, faculty and staff were conducted and analyzed. Most PRIME-US students came from socioeconomically disadvantaged backgrounds and ethnic backgrounds underrepresented in medicine, and all were committed to caring for underserved populations. The PRIME-US students experienced many program benefits including peer support, professional role models and mentorship, and curricular enrichment activities that developed their knowledge, skills, and sustained commitment to care for underserved populations. Non-PRIME students, faculty, and staff also benefited from participating in PRIME-sponsored seminars and community-based activities

Exercise in patients with inflammatory bowel diseases: current perspectives.

PubMed

Engels, Michael; Cross, Raymond K; Long, Millie D

2018-01-01

Inflammatory bowel diseases (IBDs), including both Crohn's disease (CD) and ulcerative colitis (UC), are chronic autoimmune diseases. Both CD and UC have relapsing and remitting courses. Although effective medical treatments exist for these chronic conditions, some patients do not respond to these traditional therapies. Patients are often left frustrated with incomplete resolution of symptoms and seek alternative or complementary forms of therapy. Patients often search for modifiable factors that could improve their symptoms or help them to maintain periods of remission. In this review, we examine both the published evidence on the benefits of exercise clinically and the pathophysiological changes associated with exercise. We then describe data on exercise patterns in patients with IBDs, potential barriers to exercise in IBDs, and the role of exercise in the development and course of IBDs. While some data support physical activity as having a protective role in the development of IBDs, the findings have not been robust. Importantly, studies of exercise in patients with mild-to-moderate IBD activity show no danger of disease or symptom exacerbation. Exercise has theoretical benefits on the immune response, and the limited available data suggest that exercise may improve disease activity, quality of life, bone mineral density, and fatigue levels in patients with IBDs. Overall, exercise is safe and probably beneficial in patients with IBDs. Evidence supporting specific exercise recommendations, including aspects such as duration and heart rate targets, is needed in order to better counsel patients with IBDs.

Patient Perspectives on the Experience of Being Newly Diagnosed with HIV in the Emergency Department/Urgent Care Clinic of a Public Hospital

PubMed Central

Christopoulos, Katerina A.; Massey, Amina D.; Lopez, Andrea M.; Hare, C. Bradley; Johnson, Mallory O.; Pilcher, Christopher D.; Fielding, Hegla; Dawson-Rose, Carol

2013-01-01

We sought to understand patient perceptions of the emergency department/urgent care (ED/UC) HIV diagnosis experience as well as factors that may promote or discourage linkage to HIV care. We conducted in-depth interviews with patients (n=24) whose HIV infection was diagnosed in the ED/UC of a public hospital in San Francisco at least six months prior and who linked to HIV care at the hospital HIV clinic. Key diagnosis experience themes included physical discomfort and limited functionality, presence of comorbid diagnoses, a wide spectrum of HIV risk perception, and feelings of isolation and anxiety. Patients diagnosed with HIV in the ED/UC may not have their desired emotional supports with them, either because they are alone or they are with family members or friends to whom they do not want to immediately disclose. Other patients may have no one they can rely on for immediate support. Nearly all participants described compassionate disclosure of test results by ED/UC providers, although several noted logistical issues that complicated the disclosure experience. Key linkage to care themes included the importance of continuity between the testing site and HIV care, hospital admission as an opportunity for support and HIV education, and thoughtful matching by linkage staff to a primary care provider. ED/UC clinicians and testing programs should be sensitive to the unique roles of sickness, risk perception, and isolation in the ED/UC diagnosis experience, as these things may delay acceptance of HIV diagnosis. The disclosure and linkage to care experience is crucial in forming patient attitudes towards HIV and HIV care, thus staff involved in disclosure and linkage activities should be trained to deliver compassionate, informed, and thoughtful care that bridges HIV testing and treatment sites. PMID:23991214

Mucosal Expression of Type 2 and Type 17 Immune Response Genes Distinguishes Ulcerative Colitis From Colon-Only Crohn's Disease in Treatment-Naive Pediatric Patients.

PubMed

Rosen, Michael J; Karns, Rebekah; Vallance, Jefferson E; Bezold, Ramona; Waddell, Amanda; Collins, Margaret H; Haberman, Yael; Minar, Phillip; Baldassano, Robert N; Hyams, Jeffrey S; Baker, Susan S; Kellermayer, Richard; Noe, Joshua D; Griffiths, Anne M; Rosh, Joel R; Crandall, Wallace V; Heyman, Melvin B; Mack, David R; Kappelman, Michael D; Markowitz, James; Moulton, Dedrick E; Leleiko, Neal S; Walters, Thomas D; Kugathasan, Subra; Wilson, Keith T; Hogan, Simon P; Denson, Lee A

2017-05-01

.333; 95% CI, 1.132-25.12). In an analysis of rectal tissues from treatment-naive pediatric patients with IBD, we observed activation of a type 2 immune response during the early course of UC. We were able to distinguish patients with UC from those with colon-only CD based on increased mucosal expression of genes that mediate type 2 and type 17 immune responses. Increased expression at diagnosis of genes that mediate a type 2 immune response is associated with response to therapy and remission in pediatric patients with UC. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Ulcerative colitis patients with an inflammatory response upon mesalazine cannot be desensitized: a randomized study.

PubMed

Buurman, Dorien J; De Monchy, Jan G R; Schellekens, Reinout C A; van der Waaij, Laurens A; Kleibeuker, Jan H; Dijkstra, Gerard

2015-04-01

Mesalazine is a key drug in the treatment of ulcerative colitis (UC). Intolerance to mesalazine has been described, including fever and gastrointestinal symptoms. Several case reports reported successful desensitization of patients with mesalazine intolerance. The aim was to assess the number of UC patients who are persistently intolerant to mesalazine after single-blinded rechallenge and to test the effectiveness of a rapid desensitization protocol in UC patients demonstrated mesalazine intolerance. This is a prospective, single-blind randomized study in UC patients who discontinued mesalazine because of intolerance. Patients with severe reactions were excluded. Eligible patients underwent a skin patch test with mesalazine followed by a single-blinded randomized crossover rechallenge with 500 mg mesalazine or placebo. Patients with symptoms upon rechallenge were admitted to the hospital for 3 days oral desensitization. Nine of the 37 identified UC patients who discontinued mesalazine because of intolerance were included. All nine patients had negative patch tests, seven patients had symptoms (fever, nausea, vomiting and diarrhea) within 2 h upon rechallenge. Four of these seven patients participated in the desensitization protocol and in none a successful desensitization could be performed. All four had an inflammatory intolerance reaction with rise in C-reactive protein. There were no elevations in serum tryptase or urinary-methylhistamine levels observed and no signs of immediate type allergic reactions, like urticaria, bronchial obstruction or anaphylaxis. We recommend not to rechallenge UC patients with an inflammatory response upon mesalazine and these patients will not benefit from a rapid desensitization protocol.

Balance of CD8+ CD28+ / CD8+ CD28- T lymphocytes is vital for patients with ulcerative colitis.

PubMed

Dai, Shi-Xue; Wu, Gang; Zou, Ying; Feng, Yan-Ling; Liu, Hong-Bo; Feng, Jin-Shan; Chi, Hong-Gang; Lv, Ru-Xi; Zheng, Xue-Bao

2013-01-01

Immune balances are important for many diseases including ulcerative colitis (UC). This study aimed to explore the role of the balance between CD8+ CD28+ and CD8+ CD28- T lymphocytes for the immunological pathogenesis of UC. Sixteen patients with UC, 16 patients with irritable bowel syndrome (IBS) and 15 healthy volunteers were enrolled. The frequencies of CD8+ CD28+ and CD8+CD28- T lymphocytes in peripheral blood and colon tissue were tested using flow cytometry and immunofluorescent, respectively. The cytokines of the two lymphocytes were detected by protein chips and ELISA. The expression of the signal transducers, the JAK3 and STAT6, as well the transcription factors, the NFATc2 and GATA3, was all detected by both western blot and immunohistochemistry. For UC patients, the frequencies of CD8+ CD28+ T lymphocytes, together with the ratios of CD8+ CD28+ / CD8+ CD28- T lymphocytes in blood and colon tissue, were significantly lower than those in both IBS patients and healthy volunteers. But the frequencies of CD8+ CD28- T lymphocytes in blood and colon tissue of the UC patients were significantly higher than the other two groups. The concentration of IL-7 and -13, and the expression of JAK3 and STAT6 in UC patients, were significantly lower when compared with the other two groups. Conversely, the concentration of IL-12p40 and -15, and the expression of GATA3 and NFATc2 in UC patients, were significantly higher than both IBS and control group. The balance of CD8+ CD28+ / CD8+ CD28- T lymphocytes plays a vital role in UC, while the balance tilt towards CD8+ CD28+ T lymphocytes is beneficial for patients with UC.

High prevalence of morphometric vertebral deformities in patients with inflammatory bowel disease.

PubMed

Heijckmann, Anna Caroline; Huijberts, Maya S P; Schoon, Erik J; Geusens, Piet; de Vries, Jolanda; Menheere, Paul P C A; van der Veer, Eveline; Wolffenbuttel, Bruce H R; Stockbrugger, Reinhold W; Dumitrescu, Bianca; Nieuwenhuijzen Kruseman, Arie C

2008-08-01

Earlier studies have documented that the prevalence of decreased bone mineral density (BMD) is elevated in patients with inflammatory bowel disease. The objective of this study was to investigate the prevalence of vertebral deformities in inflammatory bowel disease patients and their relation with BMD and bone turnover. One hundred and nine patients with Crohn's disease (CD) and 72 with ulcerative colitis (UC) (age 44.5+/-14.2 years) were studied. BMD of the hip (by dual X-ray absorptiometry) was measured and a lateral single energy densitometry of the spine for assessment of vertebral deformities was performed. Serum markers of bone resorption (carboxy-terminal cross-linked telopeptide of type I collagen) and formation (procollagen type I amino-terminal propeptide) were measured, and determinants of prevalent vertebral deformities were assessed using logistic regression analysis. Vertebral deformities were found in 25% of both CD and UC patients. Comparing patients with and without vertebral deformities, no significant difference was found between Z-scores and T-scores of BMD, or levels of serum carboxy-terminal cross-linked telopeptide of type I collagen and serum procollagen type I amino-terminal propeptide. Using logistic regression analysis the only determinant of any morphometric vertebral deformity was sex. The presence of multiple vertebral deformities was associated with older age and glucocorticoid use. The prevalence of morphometric vertebral deformities is high in CD and UC. Male sex, but neither disease activity, bone turnover markers, clinical risk factors, nor BMD predicted their presence. The determinants for having more than one vertebral deformity were age and glucocorticoid use. This implies that in addition to screening for low BMD, morphometric assessment of vertebral deformities is warranted in CD and UC.

Health Literacy in Orthopaedic Trauma Patients.

PubMed

Cosic, Filip; Kimmel, Lara; Edwards, Elton

2017-03-01

This study aimed to determine the level of health literacy in a postoperative orthopaedic trauma population and to evaluate the efficacy of a simple predischarge discussion strategy, targeted at improving health literacy. A pre-post intervention study was conducted from April 2014 to January 2015. Academic Level 1 trauma center. One hundred ninety consecutive orthopaedic trauma patients with operatively managed lower limb fractures were recruited. All eligible participants agreed to participate. The first ninety-nine patients received usual care (UC). The following 91 patients received a structured predischarge discussion, including x-rays, written and verbal information, from the orthopaedic staff (DG). Patients were then randomized into health literacy evaluation before first outpatient review or after first outpatient review. The primary outcome measure was a questionnaire determining health literacy. Ninety-six (97%) of the UC patients and 87 (96%) of the discussion patients (DG) completed the interview. UC preoutpatient (n = 46) demonstrated a mean score of 4.67 of a maximum 8. UC postoutpatient (n = 50) demonstrated a mean score of 5.42. DG preoutpatient (n = 47) demonstrated a mean score of 6.70. DG postoutpatient (n = 40) demonstrated a mean score of 7.08. Australian orthopaedic trauma patients demonstrate poor health literacy, with this not showing improvement after their first outpatient follow-up visit. The use of a time efficient, structured predischarge discussion improved patient health literacy. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Structural studies of the cell wall polysaccharide from Lactococcus lactis UC509.9.

PubMed

Vinogradov, Evgeny; Sadovskaya, Irina; Grard, Thierry; Murphy, James; Mahony, Jennifer; Chapot-Chartier, Marie-Pierre; van Sinderen, Douwe

2018-05-22

Lactococcus lactis is the most widely utilised starter bacterial species in dairy fermentations. The L. lactis cell envelope contains polysaccharides, which, among other known functions, serve as bacteriophage receptors. Our previous studies have highlighted the structural diversity of these so-called cell wall polysaccharides (CWPSs) among L. lactis strains that could account for the narrow host range of most lactococcal bacteriophages. In the present work, we studied the CWPS of L. lactis strain UC509.9, an Irish dairy starter strain that is host to the temperate and well-characterized P335-type phage Tuc2009. The UC509.9 CWPS structure was analyzed by methylation, deacetylation/deamination, Smith degradation and 2D NMR spectroscopy. The CWPS consists of a linear backbone composed of a tetrasaccharide repeat unit, partially substituted with a branched phosphorylated oligosaccharide having a common trisaccharide and three non-stoichiometric substitutions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Examination of electromagnetic powers with the example of a uc(Faraday) disc dynamo

NASA Astrophysics Data System (ADS)

Reich, Felix A.; Müller, Wolfgang H.

2018-03-01

This paper studies the mathematical form of electromagnetic powers and their influence on the balance of energy by using the example of a uc(Faraday) disc. First, two forms of energy (and balances thereof) are discussed. These employ different forms of powers, which can be distinguished w.r.t. their physical origins and their interpretations in context with the notions of supply and production. The stationary uc(Faraday) disc experiment is modeled following the description by Kovetz (Electromagnetic theory, Oxford University Press, Oxford, 2000). Concepts for formulating the electromagnetic field equations for the rotating disc are discussed, and the corresponding approximate analytical solutions are presented. Based on the obtained electromagnetic fields, the powers of the disc are analyzed for a stationary process. The conversion of mechanical power to heating and electromagnetic powering of an external resistor is explained. The paper concludes with the computation of the time evolution of the angular velocity for a magnetically induced breaking process of the disc.

Patient Satisfaction with Different Interpreting Methods: A Randomized Controlled Trial

PubMed Central

Leng, Jennifer; Shapiro, Ephraim; Abramson, David; Motola, Ivette; Shield, David C.; Changrani, Jyotsna

2007-01-01

Background Growth of the foreign-born population in the U.S. has led to increasing numbers of limited-English-proficient (LEP) patients. Innovative medical interpreting strategies, including remote simultaneous medical interpreting (RSMI), have arisen to address the language barrier. This study evaluates the impact of interpreting method on patient satisfaction. Methods 1,276 English-, Spanish-, Mandarin-, and Cantonese-speaking patients attending the primary care clinic and emergency department of a large New York City municipal hospital were screened for enrollment in a randomized controlled trial. Language-discordant patients were randomized to RSMI or usual and customary (U&C) interpreting. Patients with language-concordant providers received usual care. Demographic and patient satisfaction questionnaires were administered to all participants. Results 541 patients were language-concordant with their providers and not randomized; 371 were randomized to RSMI, 167 of whom were exposed to RSMI; and 364 were randomized to U&C, 198 of whom were exposed to U&C. Patients randomized to RSMI were more likely than those with U&C to think doctors treated them with respect (RSMI 71%, U&C 64%, p < 0.05), but they did not differ in other measures of physician communication/care. In a linear regression analysis, exposure to RSMI was significantly associated with an increase in overall satisfaction with physician communication/care (β 0.10, 95% CI 0.02–0.18, scale 0–1.0). Patients randomized to RSMI were more likely to think the interpreting method protected their privacy (RSMI 51%, U&C 38%, p < 0.05). Patients randomized to either arm of interpretation reported less comprehension and satisfaction than patients in language-concordant encounters. Conclusions While not a substitute for language-concordant providers, RSMI can improve patient satisfaction and privacy among LEP patients. Implementing RSMI should be considered an important component of a multipronged

Scintigraphic assessment of indium-111-labeled granulocyte splenic pooling: A new approach to inflammatory bowel disease activity

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

Loreal, O.; Moisan, A.; Bretagne, J.F.

1990-09-01

We have conducted a prospective study into the sensitivity and the specificity of the fall in splenic activity (FSA) as an index of activity in inflammatory bowel disease (IBD). FSA was measured on scintiscans obtained at 3 and 24 hr postinjection of indium-111-labeled granulocytes. One hundred and twenty-two scans were acquired in 96 patients who were divided into six groups: Gr. I = normal volunteers (n = 10); Gr. II = inflammatory rheumatism (n = 10); Gr. III = abscesses (n = 17); Gr. IV = ulcerative colitis (UC: n = 23); Gr. V = colonic Crohn's disease (CCD: nmore » = 22); and Gr. VI = ileal Crohn's disease (ICD: n = 14). FSA for Groups I and II was constantly below 10%, but it was increased in the other four groups (abscesses: 39% +/- 12%; UC: 35% +/- 13.5%; CCD: 23.7% +/- 14.7%; ICD: 21.5% +/- 11.7%). There was a significant correlation between fecal excretion of 111In (FEI) and FSA in patients with IBD (UC: r = 0.71, p less than 0.001; CCD: r = 0.74, p less than 0.001; ICD: r = 0.43, p less than 0.001). FSA was followed in 16 patients with IBD after medical treatment and there was a significant correlation between variations in FSA and in FEI (r = 0.879, p less than 0.001). FSA is a very sensitive although nonspecific index of disease activity in IBD and may replace FEI in the assessment of IBD activity.« less

Role and mechanisms of action of Escherichia coli Nissle 1917 in the maintenance of remission in ulcerative colitis patients: An update

PubMed Central

Scaldaferri, Franco; Gerardi, Viviana; Mangiola, Francesca; Lopetuso, Loris Riccardo; Pizzoferrato, Marco; Petito, Valentina; Papa, Alfredo; Stojanovic, Jovana; Poscia, Andrea; Cammarota, Giovanni; Gasbarrini, Antonio

2016-01-01

Ulcerative colitis (UC) is a chronic inflammatory disease, whose etiology is still unclear. Its pathogenesis involves an interaction between genetic factors, immune response and the “forgotten organ”, Gut Microbiota. Several studies have been conducted to assess the role of antibiotics and probiotics as additional or alternative therapies for Ulcerative Colitis. Escherichia coli Nissle (EcN) is a nonpathogenic Gram-negative strain isolated in 1917 by Alfred Nissle and it is the active component of microbial drug Mutaflor® (Ardeypharm GmbH, Herdecke, Germany and EcN, Cadigroup, In Italy) used in many gastrointestinal disorder including diarrhea, uncomplicated diverticular disease and UC. It is the only probiotic recommended in ECCO guidelines as effective alternative to mesalazine in maintenance of remission in UC patients. In this review we propose an update on the role of EcN 1917 in maintenance of remission in UC patients, including data about efficacy and safety. Further studies may be helpful for this subject to further the full use of potential of EcN. PMID:27350728

Clinical and economic outcomes in a population-based European cohort of 948 ulcerative colitis and Crohn's disease patients by Markov analysis.

PubMed

Odes, S; Vardi, H; Friger, M; Esser, D; Wolters, F; Moum, B; Waters, H; Elkjaer, M; Bernklev, T; Tsianos, E; O'Morain, C; Stockbrügger, R; Munkholm, P; Langholz, E

2010-04-01

Forecasting clinical and economic outcomes in ulcerative colitis (UC) and Crohn's disease (CD) patients is complex, but necessary. To determine: the frequency of treatment-classified clinical states; the probability of transition between states; and the economic outcomes. Newly diagnosed UC and CD patients, allocated into seven clinical states by medical and surgical treatments recorded in serial 3-month cycles, underwent Markov analysis. Over 10 years, 630 UC and 318 CD patients had 22,823 and 11,871 cycles. The most frequent clinical outcomes were medical/surgical remission (medication-free) and mild disease (on 5-aminosalicylates, antibiotics, topical corticosteroids), comprising 28% and 62% of UC cycles and 24% and 51% of CD cycles respectively. The probability of drug-response in patients receiving systemic corticosteroids/immunomodulators was 0.74 in UC, 0.66 in CD. Both diseases had similar likelihood of persistent drug-dependency or drug-refractoriness. Surgery was more probable in CD, 0.20, than UC, 0.08. In terms of economic outcomes, surgery was costlier in UC per cycle, but the outlay over 10 years was greater in CD. Drug-refractory UC and CD cases engendered high costs in the cohort. Most patients on 5-aminosalicylates, corticosteroids and immunomodulators had favourable clinical and economic outcomes over 10 years. Drug-refractory and surgical patients exhibited greater long-term expenses.

Oleuropein Decreases Cyclooxygenase-2 and Interleukin-17 Expression and Attenuates Inflammatory Damage in Colonic Samples from Ulcerative Colitis Patients

PubMed Central

Larussa, Tiziana; Oliverio, Manuela; Suraci, Evelina; Greco, Marta; Placida, Roberta; Gervasi, Serena; Marasco, Raffaella; Imeneo, Maria; Paolino, Donatella; Tucci, Luigi; Gulletta, Elio; Fresta, Massimo; Procopio, Antonio; Luzza, Francesco

2017-01-01

Oleuropein (OLE) is the major phenolic secoiridoid of olive tree leaves, and its antioxidant and anti-inflammatory activities have been demonstrated in in vitro and in vivo animal models. The aim of this study was to investigate the activity of OLE in the colonic mucosa from patients with ulcerative colitis (UC). Biopsies obtained during colonoscopy from 14 patients with active UC were immediately placed in an organ culture chamber and challenged with lipopolysaccharide from Escherichia coli (EC-LPS) at 1 μg/mL in the presence or absence of 3 mM OLE. The expression of cyclooxygenase (COX)-2 and interleukin (IL)-17 was assessed in total protein extracts from treated colonic biopsies by Western blotting. Levels of IL-17 were also measured in culture supernatant by ELISA. A microscopic evaluation of the cultured biopsies was performed by conventional histology and immunohistochemistry. The expression of COX-2 and IL-17 were significantly lower in samples treated with OLE + EC-LPS compared with those treated with EC-LPS alone (0.80 ± 0.15 arbitrary units (a.u.) vs. 1.06 ± 0.19 a.u., p = 0.003, and 0.71 ± 0.08 a.u. vs. 1.26 ± 0.42 a.u., p = 0.03, respectively) as were the levels of IL-17 in culture supernatants of OLE + EC-LPS treated colonic samples (21.16 ± 8.64 pg/mL vs. 40.67 ± 9.24 pg/mL, p = 0.01). Histologically, OLE-treated colonic samples showed an amelioration of inflammatory damage with reduced infiltration of CD3, CD4, and CD20 cells, while CD68 numbers increased. The anti-inflammatory activity of OLE was demonstrated in colonic biopsies from UC patients. These new data support a potential role of OLE in the treatment of UC. PMID:28420140

Oleuropein Decreases Cyclooxygenase-2 and Interleukin-17 Expression and Attenuates Inflammatory Damage in Colonic Samples from Ulcerative Colitis Patients.

PubMed

Larussa, Tiziana; Oliverio, Manuela; Suraci, Evelina; Greco, Marta; Placida, Roberta; Gervasi, Serena; Marasco, Raffaella; Imeneo, Maria; Paolino, Donatella; Tucci, Luigi; Gulletta, Elio; Fresta, Massimo; Procopio, Antonio; Luzza, Francesco

2017-04-15

Oleuropein (OLE) is the major phenolic secoiridoid of olive tree leaves, and its antioxidant and anti-inflammatory activities have been demonstrated in in vitro and in vivo animal models. The aim of this study was to investigate the activity of OLE in the colonic mucosa from patients with ulcerative colitis (UC). Biopsies obtained during colonoscopy from 14 patients with active UC were immediately placed in an organ culture chamber and challenged with lipopolysaccharide from Escherichia coli (EC-LPS) at 1 μg/mL in the presence or absence of 3 mM OLE. The expression of cyclooxygenase (COX)-2 and interleukin (IL)-17 was assessed in total protein extracts from treated colonic biopsies by Western blotting. Levels of IL-17 were also measured in culture supernatant by ELISA. A microscopic evaluation of the cultured biopsies was performed by conventional histology and immunohistochemistry. The expression of COX-2 and IL-17 were significantly lower in samples treated with OLE + EC-LPS compared with those treated with EC-LPS alone (0.80 ± 0.15 arbitrary units (a.u.) vs. 1.06 ± 0.19 a.u., p = 0.003, and 0.71 ± 0.08 a.u. vs. 1.26 ± 0.42 a.u., p = 0.03, respectively) as were the levels of IL-17 in culture supernatants of OLE + EC-LPS treated colonic samples (21.16 ± 8.64 pg/mL vs. 40.67 ± 9.24 pg/mL, p = 0.01). Histologically, OLE-treated colonic samples showed an amelioration of inflammatory damage with reduced infiltration of CD3, CD4, and CD20 cells, while CD68 numbers increased. The anti-inflammatory activity of OLE was demonstrated in colonic biopsies from UC patients. These new data support a potential role of OLE in the treatment of UC.

Histological Disease Activity as a Predictor of Clinical Relapse Among Patients With Ulcerative Colitis: Systematic Review and Meta-Analysis.

PubMed

Park, Sunhee; Abdi, Tsion; Gentry, Mark; Laine, Loren

2016-12-01

Endoscopic remission in ulcerative colitis (UC) is associated with improved clinical outcomes. We assessed whether histological remission predicts clinical outcomes, estimated the magnitude of effect, and determined whether histological remission provides additional prognostic utility beyond clinical or endoscopic remission. Bibliographic databases were searched for studies in inflammatory bowel disease providing baseline histological status and relation to an outcome of clinical relapse or exacerbation. Our primary analysis compared the proportion of patients with study-defined histological remission vs. the proportion with histological activity who developed clinical relapse/exacerbation. Additional analyses compared the proportion with relapse/exacerbation for the presence vs. absence of different histological features and for histological remission vs. endoscopic remission and clinical remission. A fixed-effect model was used for meta-analysis, with a random-effects model if statistical heterogeneity was present. Fifteen studies met inclusion criteria. The major methodological shortcoming was lack of blinding of the assessor of clinical relapse/exacerbation to baseline histological status in 13 of the 15 studies. Relapse/exacerbation was less frequent with baseline histological remission vs. histological activity (relative risk (RR)=0.48, 95% confidence interval (CI) 0.39-0.60) and vs. baseline clinical and endoscopic remission (RR=0.81, 95% CI 0.70-0.94). Relapse/exacerbation was also less common in the absence vs. presence of specific histological features: neutrophils in epithelium (RR=0.32, 95% CI 0.23-0.45), neutrophils in lamina propria (RR=0.43, 95% CI 0.32-0.59), crypt abscesses (RR=0.38, 95% CI 0.27-0.54), eosinophils in the lamina propria (RR=0.43, 95% CI 0.21-0.91), and chronic inflammatory cell infiltrate (RR=0.28, 95% CI 0.10-0.75). Histological remission was present in 964 (71%) of the 1360 patients with combined endoscopic and clinical remission

When Should Ulcerative Colitis Patients Undergo Colectomy for Dysplasia? Mismatch Between Patient Preferences and Physician Recommendations

PubMed Central

Siegel, Corey A.; Schwartz, Lisa M.; Woloshin, Steven; Cole, Elisabeth B.; Rubin, David T.; Vay, Tegan; Baars, Judith; Sands, Bruce E.

2010-01-01

Background If dysplasia is found on biopsies during surveillance colonoscopy for ulcerative colitis (UC), many experts recommend colectomy given the substantial risk of synchronous colon cancer. The objective was to learn if UC patients’ perceptions of their colon cancer risk and if their preferences for elective colectomy match with physicians’ recommendations if dysplasia was found. Methods A self-administered written survey included 199 patients with UC for at least 8 years (mean age 49 years, 52% female) who were recruited from Dartmouth-Hitchcock (n = 104) and the University of Chicago (n = 95). The main outcome was the proportion of patients who disagree with physicians’ recommendations for colectomy because of dysplasia. Results Almost all respondents recognized that UC raised their chance of getting colon cancer. In all, 74% thought it was “unlikely” or “very unlikely” to get colon cancer within the next 10 years and they quantified this risk to be 23%; 60% of patients would refuse a physician’s recommendation for elective colectomy if dysplasia was detected, despite being told that they had a 20% risk of having cancer now. On average, these patients would only agree to colectomy if their risk of colon cancer “right now” were at least 73%. Conclusions UC patients recognize their increased risk of colon cancer and undergo frequent surveillance to reduce their risk. Nonetheless, few seem prepared to follow standard recommendations for elective colectomy if dysplasia is found. This may reflect the belief that surveillance alone is sufficient to reduce their colon cancer risk or genuine disagreement about when it is worth undergoing colectomy. PMID:20186940

Irritable bowel syndrome-type symptoms in patients with inflammatory bowel disease: a real association or reflection of occult inflammation?

PubMed

Keohane, John; O'Mahony, Caitlin; O'Mahony, Liam; O'Mahony, Siobhan; Quigley, Eamonn M; Shanahan, Fergus

2010-08-01

Do gastrointestinal symptoms in patients with inflammatory bowel disease (IBD) in apparent remission reflect the coexistence of irritable bowel syndrome (IBS) or subclinical inflammation? The aims of this study were as follows: (i) to prospectively determine the prevalence of IBS symptoms in IBD patients in remission; and (ii) to determine whether IBS symptoms correlate with levels of fecal calprotectin. Remission was defined by physician assessment: Crohn's disease (CD) activity index activity index patients and by 17/44 (38.6%) of those with ulcerative colitis (UC). However, fecal calprotectin was significantly elevated above the upper limit of normal in both IBD patient groups, indicating the presence of occult inflammation. Furthermore, calprotectin levels were significantly higher in CD and UC patients with criteria for IBS than in those without IBS-type symptoms. QOL scores were lower and HAD scores higher among UC patients with IBS symptoms in comparison to those who did not have IBS symptoms. IBS-like symptoms are common in patients with IBD who are thought to be in clinical remission, but abnormal calprotectin levels suggest that the mechanism in most cases is likely to be occult inflammation rather than coexistent IBS.

Evidence to Support Monitoring of Vedolizumab Trough Concentrations in Patients With Inflammatory Bowel Diseases.

PubMed

Dreesen, Erwin; Verstockt, Bram; Bian, Sumin; de Bruyn, Magali; Compernolle, Griet; Tops, Sophie; Noman, Maja; Van Assche, Gert; Ferrante, Marc; Gils, Ann; Vermeire, Séverine

2018-04-25

Trough concentrations of vedolizumab were found to correlate with clinical response in phase 3 studies of patients with ulcerative colitis (UC) or Crohn's disease (CD). Nevertheless, there are no solid data to support monitoring of vedolizumab trough concentrations in treated patients. We investigated the correlation between vedolizumab exposure and response in a real-world population and aimed to identify patient factors that affect exposure and response. We performed a retrospective cohort study of 179 consecutive patients (66 with UC and 113 with CD) who began vedolizumab therapy from September 1, 2015, through October 1, 2016, at University Hospitals Leuven, Belgium. Serum concentrations of vedolizumab were measured before all infusions up to week 30. Effectiveness endpoints included endoscopic healing (UC, Mayo endoscopic sub-score ≤1; CD, absence of ulcers), clinical response (physicians' global assessment), and biologic response or remission (based on level of C-reactive protein) and were assessed at week 14 (for patients with UC) and week 22 (for patients with CD). A stepwise forward addition-backward elimination modeling approach was performed to identify factors independently associated with vedolizumab exposure and response. Vedolizumab trough concentrations >30.0 μg/mL at week 2, >24.0 μg/mL at week 6, and >14.0 μg/mL during maintenance therapy associated with a higher probability of attaining the effectiveness endpoints for patients with UC or CD (P < .05). Higher body mass and more severe disease (based on high level of C-reactive protein and low level of albumin and/or hemoglobin) at the start of vedolizumab therapy associated with lower trough concentrations of vedolizumab over the 30-week period and a lower probability of achieving mucosal healing (P < .05). Mucosal healing was achieved in significantly more patients with UC than patients with CD, even though a diagnosis of UC was not an independent predictor of higher vedolizumab trough

High Dephosphorylated-Uncarboxylated MGP in Hemodialysis patients: risk factors and response to vitamin K2, A pre-post intervention clinical trial.

PubMed

Aoun, Mabel; Makki, Maha; Azar, Hiba; Matta, Hiam; Chelala, Dania Nehme

2017-06-07

Vascular calcifications are highly prevalent in hemodialysis patients. Dephosphorylated-uncarboxylated MGP (dp-ucMGP) was found to increase in vitamin K-deficient patients and may be associated with vascular calcifications. Supplementation of hemodialysis patients with vitamin K 2 (menaquinone-7) has been studied in Europe with a maximum 61% drop of dp-ucMGP levels. The aim of this study is to assess first the drop of dp-ucMGP in an Eastern Mediterranean cohort after vitamin K 2 treatment and second the correlation between baseline dp-ucMGP and vascular calcification score. This is a prospective, pre-post intervention clinical trial involving 50 hemodialysis patients who received daily 360 μg of menaquinone-7 for 4 weeks. At baseline they were assessed for plasma dp-ucMGP levels and vascular calcification scores (AC-24) as well as for other demographic, clinical and biological variables. Dp-ucMGP levels were measured a second time at 4 weeks. At baseline, dp-ucMGP levels were extremely elevated with a median of 3179.15 (1825.25; 4339.50) pM and correlated significantly with AC-24 (Spearman's rho = 0.43, P = 0.002). Using a bivariate regression analysis, the association between dp-ucMGP levels and AC-24 was most significant when comparing dp-ucMGP levels less than 1000 to those more than 1000 pM (P = 0.02). Dp-ucMGP levels higher than 5000 pM were significantly associated with females, patients with recent fracture and patients with lower serum albumin (respectively P = 0.02, 0.004 and 0.046). The average drop of dp-ucMGP at 4 weeks of treatment was found to be 86% with diabetics having the lowest drop rate (P = 0.01). Vitamin K deficiency, as assessed by high dp-ucMGP levels, is profound in hemodialysis patients from the Eastern Mediterranean region and it is significantly correlated with vascular calcifications. Daily 360 μg of menaquinone-7, given for 4 weeks, effectively reduces dp-ucMGP in this population. Future studies are needed to assess

Internet-orientated Assessment of QOL and Actual Treatment Status in Japanese Patients with Inflammatory Bowel Disease: The 3I survey.

PubMed

Matsumoto, Takayuki; Yanai, Shunichi; Toya, Yosuke; Ueno, Masato; Nakamura, Shotaro

2015-06-01

This survey aimed to compare actual lifestyle factors and QOL between Japanese IBD patients and healthy Japanese controls, by questionnaire using an internet-web system. Through the internet-web system, we asked 464 patients with Crohn's disease [CD], 360 patients with ulcerative colitis [UC], and 4100 healthy controls to answer a questionnaire including an eight-item short-form health survey [SF-8]. The survey was conducted until data had been accumulated from the predetermined numbers of patients [120 patients each with CD and UC] and healthy controls [240 subjects]. QOL assessment by SF-8 revealed scores for six of the eight subscale items and the summary score for the mental component to be significantly lower in the CD and UC groups than in controls. There was a significant negative correlation between each SF-8 score and the degree of CD and UC symptoms. The marriage rate in adult patients was significantly lower in the CD than in the UC group or the controls. The mean annual income and the employment rate were significantly lower in the CD than in the UC group or the controls. CD patients receiving biologicals were more frequently satisfied with the efficacy of treatment than UC patients were with their treatment regimens [56% vs 29%]. Actual lifestyle factors and QOL appear to be impaired in Japanese patients with IBD, especially those with CD. The subjective efficacy of biologicals might be greater in CD than in UC. 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.

Molecular profiling of mucosal tissue associated microbiota in patients manifesting acute exacerbations and remission stage of ulcerative colitis.

PubMed

Walujkar, Sandeep A; Kumbhare, Shreyas V; Marathe, Nachiket P; Patangia, Dhrati V; Lawate, Parimal S; Bharadwaj, Renu S; Shouche, Yogesh S

2018-05-23

Dysbiosis of intestinal microflora has been postulated in ulcerative colitis (UC), which is characterized by imbalance of mucosal tissue associated bacterial communities. However, the specific changes in mucosal microflora during different stages of UC are still unknown. The aim of the current study was to investigate the changes in mucosal tissue associated microbiota during acute exacerbations and remission stages of UC. The mucosal microbiota associated with colon biopsy of 12 patients suffering from UC (exacerbated stage) and the follow-up samples from the same patients (remission stage) as well as non-IBD subjects was studied using 16S rRNA gene-based sequencing and quantitative PCR. The total bacterial count in patients suffering from exacerbated phase of UC was observed to be two fold lower compared to that of the non-IBD subjects (p = 0.0049, Wilcox on matched-pairs signed rank tests). Bacterial genera including Stenotrophomonas, Parabacteroides, Elizabethkingia, Pseudomonas, Micrococcus, Ochrobactrum and Achromobacter were significantly higher in abundance during exacerbated phase of UC as compared to remission phase. The alterations in bacterial diversity with an increase in the abnormal microbial communities signify the extent of dysbiosis in mucosal microbiota in patients suffering from UC. Our study helps in identifying the specific genera dominating the microbiota during the disease and thus lays a basis for further investigation of the possible role of these bacteria in pathogenesis of UC.

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

Consecutive monitoring of faecal calprotectin during mesalazine suppository therapy for active rectal inflammation in ulcerative colitis.

PubMed

Yamamoto, T; Shimoyama, T; Matsumoto, K

2015-09-01

No studies have monitored the levels of faecal calprotectin (FC) during mesalazine suppository therapy for proctitis in ulcerative colitis (UC). To evaluate the value of consecutive monitoring of FC in patients with UC during mesalazine suppository therapy. One hundred and sixty patients with active inflammation limited to the rectum were treated with mesalazine 1 g suppository once daily for 8 weeks. Patients who achieved clinical remission were advised to maintain the treatment, and were followed up for further 40 weeks. FC levels were measured every 8 weeks during the study. At week 8, 118 patients (74%) went into clinical remission, of whom 88 achieved endoscopic healing. The median FC level significantly decreased in patients with clinical and endoscopic remission (both P < 0.0001), while it did not change significantly in those without remission. Eighty (68%) of the 118 patients with remission continued the treatment. Twenty-four patients (30%) relapsed during the 40-week follow-up. In patients with clinical relapse, the median FC level elevated already 8 weeks before the diagnosis of relapse. In contrast, in patients who maintained remission it remained at a low level and did not significantly change during the follow-up. Elevated FC level (≥55 μg/g) was useful for the early diagnosis of relapse (88% sensitivity and 80% specificity). Faecal calprotectin may represent a useful biomarker for the assessment of disease activity in UC patients treated with mesalazine suppositories. Serial monitoring of faecal calprotectin appears to be valuable for the prediction and early diagnosis of relapse during maintenance therapy. © 2015 John Wiley & Sons Ltd.

Usefulness of Transcriptional Blood Biomarkers as a Non-invasive Surrogate Marker of Mucosal Healing and Endoscopic Response in Ulcerative Colitis.

PubMed

Planell, Núria; Masamunt, M Carme; Leal, Raquel Franco; Rodríguez, Lorena; Esteller, Miriam; Lozano, Juan J; Ramírez, Anna; Ayrizono, Maria de Lourdes Setsuko; Coy, Claudio Saddy Rodrigues; Alfaro, Ignacio; Ordás, Ingrid; Visvanathan, Sudha; Ricart, Elena; Guardiola, Jordi; Panés, Julián; Salas, Azucena

2017-10-27

Ulcerative colitis [UC] is a chronic inflammatory disease of the colon. Colonoscopy remains the gold standard for evaluating disease activity, as clinical symptoms are not sufficiently accurate. The aim of this study is to identify new accurate non-invasive biomarkers based on whole-blood transcriptomics that can predict mucosal lesions and response to treatment in UC patients. Whole-blood samples were collected for a total of 152 UC patients at endoscopy. Blood RNA from 25 UC individuals and 20 controls was analysed using microarrays. Genes that correlated with endoscopic activity were validated using real-time polymerase chain reaction in an independent group of 111 UC patients, and a prediction model for mucosal lesions was evaluated. Responsiveness to treatment was assessed in a longitudinal cohort of 16 UC patients who started anti-tumour necrosis factor [TNF] therapy and were followed up for 14 weeks. Microarray analysis identified 122 genes significantly altered in the blood of endoscopically active UC patients. A significant correlation with the degree of endoscopic activity was observed in several genes, including HP, CD177, GPR84, and S100A12. Using HP as a predictor of endoscopic disease activity, an accuracy of 67.3% was observed, compared with 52.4%, 45.2%, and 30.3% for C-reactive protein, erythrocyte sedimentation rate, and platelet count, respectively. Finally, at 14 weeks of treatment, response to anti-TNF therapy induced alterations in blood HP, CD177, GPR84, and S100A12 transcripts that correlated with changes in endoscopic activity. Transcriptional changes in UC patients are sensitive to endoscopic improvement and appear to be an effective tool to monitor patients over time. © European Crohn’s and Colitis Organisation (ECCO) 2017.

Usefulness of Transcriptional Blood Biomarkers as a Non-invasive Surrogate Marker of Mucosal Healing and Endoscopic Response in Ulcerative Colitis

PubMed Central

Planell, Núria; Masamunt, M Carme; Leal, Raquel Franco; Rodríguez, Lorena; Esteller, Miriam; Lozano, Juan J; Ramírez, Anna; Ayrizono, Maria de Lourdes Setsuko; Coy, Claudio Saddy Rodrigues; Alfaro, Ignacio; Ordás, Ingrid; Visvanathan, Sudha; Ricart, Elena; Guardiola, Jordi; Panés, Julián; Salas, Azucena

2017-01-01

Abstract Background and Aims Ulcerative colitis [UC] is a chronic inflammatory disease of the colon. Colonoscopy remains the gold standard for evaluating disease activity, as clinical symptoms are not sufficiently accurate. The aim of this study is to identify new accurate non-invasive biomarkers based on whole-blood transcriptomics that can predict mucosal lesions and response to treatment in UC patients. Methods Whole-blood samples were collected for a total of 152 UC patients at endoscopy. Blood RNA from 25 UC individuals and 20 controls was analysed using microarrays. Genes that correlated with endoscopic activity were validated using real-time polymerase chain reaction in an independent group of 111 UC patients, and a prediction model for mucosal lesions was evaluated. Responsiveness to treatment was assessed in a longitudinal cohort of 16 UC patients who started anti-tumour necrosis factor [TNF] therapy and were followed up for 14 weeks. Results Microarray analysis identified 122 genes significantly altered in the blood of endoscopically active UC patients. A significant correlation with the degree of endoscopic activity was observed in several genes, including HP, CD177, GPR84, and S100A12. Using HP as a predictor of endoscopic disease activity, an accuracy of 67.3% was observed, compared with 52.4%, 45.2%, and 30.3% for C-reactive protein, erythrocyte sedimentation rate, and platelet count, respectively. Finally, at 14 weeks of treatment, response to anti-TNF therapy induced alterations in blood HP, CD177, GPR84, and S100A12 transcripts that correlated with changes in endoscopic activity. Conclusions Transcriptional changes in UC patients are sensitive to endoscopic improvement and appear to be an effective tool to monitor patients over time. PMID:28981629

Draft Genome Sequence of Vancomycin-Heteroresistant Staphylococcus epidermidis Strain UC7032, Isolated from Food

PubMed Central

Pietta, Ester; Bassi, Daniela; Fontana, Cecilia; Puglisi, Edoardo; Cappa, Fabrizio; Cocconcelli, Pier Sandro

2013-01-01

Staphylococcus epidermidis strain UC7032 was isolated from ready-to-eat cured meat and is heteroresistant to glycopeptide antibiotics. The draft whole-genome analysis revealed that this strain shows common characteristics typical of strains that are involved in nosocomial infections. PMID:24072859

Chronic obstructive pulmonary disease self-management activation research trial (COPD-SMART): results of recruitment and baseline patient characteristics.

PubMed

Russo, Rennie; Coultas, David; Ashmore, Jamile; Peoples, Jennifer; Sloan, John; Jackson, Bradford E; Uhm, Minyong; Singh, Karan P; Blair, Steven N; Bae, Sejong

2015-03-01

To describe the recruitment methods, study participation rate, and baseline characteristics of a representative sample of outpatients with COPD eligible for pulmonary rehabilitation participating in a trial of a lifestyle behavioral intervention to increase physical activity. A patient registry was developed for recruitment using an administrative database from primary care and specialty clinics of an academic medical center in northeast Texas for a parallel group randomized trial. The registry was comprised of 5582 patients and over the course of the 30 month recruitment period 325 patients were enrolled for an overall study participation rate of 35.1%. After a 6-week COPD self-management education period provided to all enrolled patients, 305 patients were randomized into either usual care (UC; n=156) or the physical activity self-management intervention (PASM; n=149). There were no clinically significant differences in demographics, clinical characteristics, or health status indicators between the randomized groups. The results of this recruitment process demonstrate the successful use of a patient registry for enrolling a representative sample of outpatients eligible for pulmonary rehabilitation with COPD from primary and specialty care. Moreover, this approach to patient recruitment provides a model for future studies utilizing administrative databases and electronic health records. Published by Elsevier Inc.

Design and synthesis of a novel multifunctional stabilizer for highly stable uc(dl)-tetrahydropalmatine nanosuspensions and in vitro study

NASA Astrophysics Data System (ADS)

Yan, Beibei; Wang, Yancai; Wang, Lulu; Zhou, Yuqi; Shang, Xueyun; Zhao, Juan; Liu, Yangyang; Du, Juan

2018-05-01

The present study aimed to prepare stable uc(dl)-tetrahydropalmatine (uc(dl)-THP) nanosuspensions of optimized formulation with PEGylated chitosan as a multifunctional stabilizer using the antisolvent precipitation method. A central composite design project of three factors and five-level full factorial (53) was applied to design the experimental program, and response surface methodology analysis was used to optimize the experimental conditions. The effects of critical influencing factors such as PEGylated chitosan concentration, operational temperature, and ultrasonic energy on particle size and zeta potential were investigated. Under the optimization nanosuspension formulation, the particle size was 269 nm and zeta potential was at 37.4 mV. Also, the uc(dl)-THP nanosuspensions maintained good physical stability after 2 months, indicating the potential ability of the multifunctional stabilizer for stable nanosuspension formulation. Hence, the present findings indicated that PEGylated chitosan could be used as the ideal stabilizer to form a physically stable nanosuspension formulation.

Medical resource utilization and associated costs in patients with ulcerative colitis in the UK: a chart review analysis.

PubMed

Bodger, Keith; Yen, Linnette; Szende, Agota; Sharma, Gunjan; Chen, Yaozhu J; McDermott, John; Hodgkins, Paul

2014-02-01

Limited evidence is available on the economic burden of ulcerative colitis (UC) in the UK, particularly relating to the impact of relapse frequency on direct medical costs. This study identifies and assesses medical resource utilization (MRU) and associated direct costs in mild and moderate UC patients in the UK. A retrospective chart review of patients with mild-to-moderate UC diagnosed at least 1 year before the study was performed. From 33 general practitioner (GP) and 34 gastroenterologist sites, charts of the last three UC patients fulfilling the inclusion criteria were reviewed. Descriptive statistics were calculated for MRU and 2011 costs (GB£) by number of relapses. The study population included 201 patients with a mean age of 39.9 years; 44% were women and the mean disease duration was 7.4 years. UC-related costs of each MRU category increased with the number of relapses. Comparing patients without relapse with those with more than two relapses, the mean annual UC-related costs were £14 versus £2556 for hospitalizations; £218 versus £988 for visits (including nurse, GP, specialist, and other visits); £21 versus £1303 for procedures; £17 versus £188 for diagnostics; and £1168 versus £6660 for all-cause total costs. Age, sex, and site of data reporting (GP vs. gastroenterologist) were not associated with MRU or costs. Patients with mild-to-moderate UC incurred considerable costs that increased markedly with the number of relapses. These findings support the importance of maintenance therapies in UC that reduce or prevent relapses. Quantifying the relationship between relapse rate and costs will inform future health economic studies.

Patients' perceptions on the impact of coffee consumption in inflammatory bowel disease: friend or foe?--a patient survey.

PubMed

Barthel, Christiane; Wiegand, Sandra; Scharl, Sylvie; Scharl, Michael; Frei, Pascal; Vavricka, Stephan R; Fried, Michael; Sulz, Michael Christian; Wiegand, Nico; Rogler, Gerhard; Biedermann, Luc

2015-08-12

Environmental factors are an integral component in the pathogenesis of inflammatory bowel disease (IBD). There is an increasing interest in nutritive components. While the potential disease-modifying role of coffee has been intensively investigated in a variety of gastrointestinal diseases, the data on the potential impact on IBD is very limited. We aimed to determine the patients' perspective on coffee consumption in IBD. We conducted a questionnaire among IBD patients in Switzerland, assessing key questions regarding coffee consumption. Descriptive statistics including chi square testing were used for analysis of questionnaire data. Among a total of 442 patients 73% regularly consume coffee. 96% of patients attributing a positive and 91% of patients attributing no impact of coffee intake on IBD regularly drink coffee and surprisingly even 49% of those patients that assign a negative impact on disease symptoms. Among those patients refraining from regular coffee intake 62% are convinced that coffee adversely influences intestinal symptoms, significantly more in Crohn's disease (CD) than in ulcerative colitis (UC) (76% vs. 44%, p = 0.002). In total, 38% of all study subjects suppose that coffee has an effect on their symptoms of disease, significantly more in CD (54%) compared to UC patients (22%, p < 0.001). Moreover, while 45% of CD patients feel that coffee has a detrimental influence, only 20% of UC patients share this impression (p < 0.001). Two thirds of IBD patients regularly consume coffee. More than twice as many CD compared to UC patients attribute a symptom-modifying effect of coffee consumption, the majority a detrimental one. However, this negative perception does not result in abstinence from coffee consumption.

LncRNA-uc002mbe.2 Interacting with hnRNPA2B1 Mediates AKT Deactivation and p21 Up-Regulation Induced by Trichostatin in Liver Cancer Cells.

PubMed

Chen, Ting; Gu, Chengxin; Xue, Cailin; Yang, Tao; Zhong, Yun; Liu, Shiming; Nie, Yuqiang; Yang, Hui

2017-01-01

Long non-coding RNAs (lncRNAs) have been implicated in liver carcinogenesis. We previously showed that the induction of lncRNA-uc002mbe.2 is positively associated with the apoptotic effect of trichostatin A (TSA) in hepatocellular carcinoma (HCC) cells. The current study further analyzed the role of uc002mbe.2 in TSA-induced liver cancer cell death. The level of uc002mbe.2 was markedly increased by TSA in the cytoplasm of HCC cells. Knockdown of uc002mbe.2 prohibited TSA-induced G2/M cell cycle arrest, p21 induction, and apoptosis of Huh7 cells and reversed the TSA-mediated decrease in p-AKT. RNA pull-down and RNA-binding protein immunoprecipitation (RIP) assays revealed that TSA induced an interaction between uc002mbe.2 and heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in Huh7 cells. This interaction mediated AKT deactivation and p21 induction in liver cancer cells. In an athymic xenograft mouse model, knockdown of uc002mbe.2 significantly prohibited the TSA-mediated reduction in tumor size and weight. In addition, the ability of TSA to reduce hnRNPA2B1 and p-AKT levels and induce p21 in the xenograft tumors was prevented by uc002mbe.2 knockdown. Therefore, the interaction of uc002mbe.2 and hnRNPA2B1 in mediating AKT deactivation and p21 induction is involved in the cytostatic effect of trichostatin in liver cancer cells.

The Relevance of Vitamin and Iron Deficiency in Patients with Inflammatory Bowel Diseases in Patients of the Swiss IBD Cohort.

PubMed

Madanchi, Matiar; Fagagnini, Stefania; Fournier, Nicolas; Biedermann, Luc; Zeitz, Jonas; Battegay, Edouard; Zimmerli, Lukas; Vavricka, Stephan R; Rogler, Gerhard; Scharl, Michael

2018-04-13

Vitamin and iron deficiencies are common in patients with inflammatory bowel disease (IBD) as a result of chronic intestinal inflammation, increase in demand, or dietary restrictions. Here, we assessed the frequency of complications in relation to deficiency of iron, folate acid, and vitamin B12 in patients enrolled in the nationwide Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). A total of 2666 patients were included in the study, 1558 with Crohn's disease (CD) and 1108 with ulcerative colitis (UC). Iron deficiency anemia was detected in 19.6% of CD patients and 21.6% of UC patients. In CD patients low BMI and nonsmoker status were positively associated with anemia. In both CD and UC, malabsorption syndrome, defined as failure of the GI tract to absorb 1 or more substances from the diet, was found to be significantly associated with anemia (6.2% and 3.8%, respectively) and current steroid use (40% CD, 52.7% UC). In CD patients with ileal (31.7% vs 20%) and colonic (29.9% vs 25%) disease location folate deficiency was significantly higher than in patients with ileocolonic CD or upper GI involvement. In CD patients, vitamin B12 deficiency was associated with the onset of stenosis and intestinal surgery (42.9% vs 32.8% and 46% vs 33% for patients with versus without B12 deficiency). Our data indicate that due to frequent occurrence of deficiency states, regular monitoring and substitution of vitamins and iron are mandatory and may prevent long-term intestinal and extraintestinal complications in IBD patients.

Lifestyle educational program strongly increases compliance to nonpharmacologic intervention in hypertensive patients: a 2-year follow-up study.

PubMed

Ferrara, Aldo L; Pacioni, Delia; Di Fronzo, Valentina; Russo, Barbara F; Staiano, Laura; Speranza, Enza; Gente, Rosaria; Gargiulo, Francesco; Ferrara, Fabio

2012-11-01

The authors investigated the efficacy of a lifestyle educational program, organized in small group meetings, in improving the outcome of a nonpharmacologic intervention. One hundred and eighty-eight hypertensive patients with stable blood pressure (BP) levels and drug therapy in the previous 6 months were randomly divided into educational care (EC) and usual care (UC) groups. They were followed at 3-month intervals up to 2 years. In addition to the visits in an outpatient clinic, patients in the EC program participated in small group meetings in order to improve their knowledge of the disease and reinforce their motivation for treatment. At baseline, EC and UC groups were similar for age, sex, body mass index (BMI), blood pressure (BP) levels, and pharmacologic treatment. Patients in the EC group had significantly reduced total energy, total and saturated fats, and sodium intake. Physical activity was significantly increased in the EC group as well. At the end of the 1-year follow-up, BMI (P<.001), visceral fat (P<.001), and BP (P<.001) were significantly lower in the EC group compared with the UC group. Pharmacologic treatment during the study was similar for all classes of drugs apart from diuretics whose dose was higher in the UC group at the end of the study. © 2012 Wiley Periodicals, Inc.

In Vitro Evaluation of Nonnucleoside Reverse Transcriptase Inhibitors UC-781 and TMC120-R147681 as Human Immunodeficiency Virus Microbicides†

PubMed Central

Van Herrewege, Yven; Michiels, Jo; Van Roey, Jens; Fransen, Katrien; Kestens, Luc; Balzarini, Jan; Lewi, Paul; Vanham, Guido; Janssen, Paul

2004-01-01

The nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 (Dapivirine) effectively prevented human immunodeficiency virus (HIV) infection in cocultures of monocyte-derived dendritic cells and T cells, representing primary targets in sexual transmission. Both drugs had a favorable therapeutic index. A 24-h treatment with 1,000 nM UC-781 or 100 nM TMC120-R147681 prevented cell-free HIV infection, whereas 10-fold-higher concentrations blocked cell-associated HIV. PMID:14693562

[Multicentric prospective randomized and controlled study assessing effectiveness of intravaginal electrostimulation at home compared to usual care in female patients with urinary incontinence and prior perineal reeducation].

PubMed

Lopès, P; Rimbault, F; Scheffler, M; André, C; Cappelletti, M-C; Marès, P

2014-11-01

In order to maintain the benefits of perineal reeducation, patients with stress urinary incontinence need to perform self-retraining exercises of the perineal muscles at home. The aim of this randomized prospective multicentric study is to assess the effectiveness of GYNEFFIK(®), a perineal electrostimulator, during this home-care phase. Two parallel groups of women with stress urinary incontinence (UI) or with mixed UI (composed predominantly of stress UI), improved by physiotherapy, have followed a self-reeducation program, either with electrostimulation sessions (GYNEFFIK(®) or home perineal electrostimulation [HPES] arm) or with usual care (UC) only, without electrostimulation. The comparison of the two groups was based on the rate of women in which the benefit of the initial perineal reeducation was maintained (defined as the ICIQ and Ditrovie scales' score not worsening) at 2, 4 and 6 months. A total of 161 patients were analyzed (76 in the HPES arm and 85 in the UC arm). The therapeutic benefit of the initial perineal reeducation at the last available measure (6 months for a wide majority of patients) was maintained in 81.6% in the HPES arm versus 62.4% in the UC arm (P=0.007). This significant difference reflects a significant improvement both in clinical symptomatology and in quality of life. ICIQ score was improved in 44% of patients of HPES arm while it was improved in 14% of patients of UC arm (P<0.001) and daily number of urine leakage decreased of 1.2 leakage in the HPES arm versus 0.1 leakage in UC arm (P<0.05). Likewise, improvement of quality of life was superior in the HPES arm (48% improvement of Ditrovie score versus 19% in the UC group ; P<0.05). Investigator global impression was more favorable in the HPES arm (clinical improvement in 83% of patients versus 68% in the UC arm). At the last measure (i.e. endpoint), the benefit of initial physiotherapy was considered maintained or improved in all patients of the HPES arm while it was reported

Ulcerative colitis in a multiracial Asian country: Racial differences and clinical presentation among Malaysian patients

PubMed Central

Tan, Yan-Mei; Goh, Khean-Lee

2005-01-01

AIM: TO determine the prevalence of ulcerative colitis (UC) in Malaysian patients and to establish the spectrum of the disease seen in Malaysian patients. METHODS: Data were obtained retrospectively from a review of the medical records of in- and out-patients with a diagnosis of UC at the University Hospital, Kuala Lumpur between 1985 and 1998. RESULTS: There were 45 confirmed cases of UC, of which 3 were foreigners, who were excluded from analysis. Thirty new cases of UC were diagnosed during the study period. Their mean age at presentation was 33.0 ± 10.0 years. The highest prevalence of UC was 17.9/100 000 hospital admissions in the Indians, followed by 11.2/100 000 hospital admissions in the Chinese. The lowest prevalence was 3.7/100 000 hospital admissions in the Malays. The prevalence of UC was significantly higher in the Indians and the Chinese when compared with the Malays with an OR of 4.89 (CI = 2.02-12.24; c2 = 15.45,P < 0.001) and 3.06 (CI = 1.24-7.78; c2 = 6.30; P = 0.012) respectively. The extent of colonic disease was similar in the Malay and Indian patients. In contrast, distal or left-sided colitis predominated in the Chinese with an OR of 8.17 (95%CI = 1.31-64.87; c2 = 5.53, P = 0.02). Extraintestinal manifestations were uncommon (11.9%). CONCLUSION: UC is an uncommon disease in Malaysia, but racial differences exist. The Indians had the highest prevalence of UC with the Chinese demonstrating the least extensive disease. PMID:16270398

Ulcerative colitis with acute pleurisy

PubMed Central

Lu, Shuming; Wang, Lihua; Zhang, Weisheng; Zhang, Zhuqing; Liu, Lina; Wang, Yingde; Meng, Hua

2017-01-01

Abstract Rationale: Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease, are associated with a large number of extraintestinal manifestations. Pulmonary manifestations are infrequently seen in patients with IBD. Moreover, serositis including pleural and pericardial manifestations in UC is rare. Patient concerns: We report a case of UC with acute pleurisy in a 43-year-old man; review literature; and discuss the diagnosis, differential diagnosis, and treatment. Diagnoses: Active duodenal ulcer was found using gastroscopy. Multiple ulcers in segmented pattern were noticed in the left hemi-colon using colonoscopy. An UC in active stage was confirmed subsequently by histology. Intervention: The patient was treated with bifidobacterium tetravaccine tablets, oral mesalazine and mesalazine enemas. The omeprazole and mucosal protective agents were given to treat the duodenal ulcer. Outcomes: As follow-up, the therapy including oral mesalazine and infliximab regularly was continued and the patient condition was stabilized. Main lesson: Pulmonary involvement should be considered in patients who develop pleurisy in UC. Infliximab is considered the better available treatment for patients presenting with pleurisy in UC. PMID:28746225

[Clinical extraintestinal manifestations in patients with ulcerative colitis].

PubMed

Toader, Elena

2007-01-01

Ulcerative colitis (UC) is a chronic disease clinically manifest either by bowel symptoms alone or extraintestinal symptoms. Our prospective study included 635 patients with ulcerative colitis (334 males and 301 females, mean age 37.54 +/- 13.84, range 20-70 years). The presence of the common extraintestinal symptoms (ES) was analyzed. Of the 635 investigated patients, these symptoms were found in 83 (13%, 49 males and 34 females, mean age 41.6 +/- 13.95 range 21-70). Patients with ES suffered longer from UC on the average, that is 60.6 years. Most commonly ES involved the joints, 38 (45.8%) patients, hepatobiliary, 28 patients (33.7%), skin, 10 patients (12%) and eyes, 7 patients (8.4%). In 18% of the patients two or more ES were present. ES were clinically detectable after the intestinal symptoms in 81% patients. An increased tendency of ES to occur in patients with a more extensive disease was noticed. The prevalence of ES in the UC patients from NE Romania is in agreement with data from other countries. The number of ES supports the need for complex follow-up in these patients.

Predictors of Clinical Response and Remission at One year among a Multicenter Cohort of Patients with Inflammatory Bowel Disease Treated with Vedolizumab

PubMed Central

Allegretti, Jessica R.; Barnes, Edward L.; Stevens, Betsey; Storm, Margaret; Ananthakrishnan, Ashwin; Yajnik, Vijay; Korzenik, Joshua

2017-01-01

Background Vedolizumab (VDZ) has demonstrated long term efficacy in Crohn’s disease (CD) and ulcerative colitis (UC) in phase III trials. Aims Our aim was to evaluate the efficacy of VDZ at week 54 in inflammatory bowel disease (IBD) in a multicenter cohort of patients. Methods Adult patients completing induction therapy with VDZ were eligible for this study. Clinical response and remission was assessed using the Harvey Bradshaw index (HBI) for CD, the simple clinical colitis activity index (SCCAI) for UC and physician assessment. Results Among 136 total patients (96 CD and 40 UC), 76 (56%) demonstrated clinical response or remission at week 54. In univariate analysis, for patients with CD concomitant initiation of immunomodulator therapy (2.71, 95% CI 1.11 – 6.57), the addition of an immunomodulator (OR 11.49, 3.16 – 41.75) and CRP <3 (4.92, 95% CI 1.99 – 12.15) were associated with increased odds of clinical response or remission at week 54. For UC patients hospitalization after VDZ induction was associated with decreased odds of response or remission at week 54 ( OR 0.22, 95%CI 0.05–0.88). On multivariate analysis in CD, addition of an immunomodulator (OR 8.33, 95% CI 2.15–32.26) remained significant predictors of clinical response or remission at week 54. Conclusions Among a multicenter cohort of patients with IBD demonstrating primary response to VDZ, the addition of combination therapy with an immunomodulator is a significant predictor of clinical response or remission at week 54 in patients with CD. PMID:28357697

Longer-term effects of home-based exercise interventions on exercise capacity and physical activity in coronary artery disease patients: A systematic review and meta-analysis.

PubMed

Claes, Jomme; Buys, Roselien; Budts, Werner; Smart, Neil; Cornelissen, Véronique A

2017-02-01

Background Exercise-based cardiovascular rehabilitation (CR) improves exercise capacity (EC), lowers cardiovascular risk profile and increases physical functioning in the short term. However, uptake of and adherence to a physically active lifestyle in the long run remain problematic. Home-based (HB) exercise programmes have been introduced in an attempt to enhance long-term adherence to recommended levels of physical activity (PA). The current systematic review and meta-analysis aimed to compare the longer-term effects of HB exercise programmes with usual care (UC) or centre-based (CB) CR in patients referred for CR. Design Systematic review and meta-analysis. Methods Non-randomised controlled trials (RCTs) or randomised trials comparing the effects of HB exercise programmes with UC or CB rehabilitation on EC and/or PA, with a follow-up period of ≥12 months and performed in coronary artery disease patients, were searched in four databases (PubMed, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Central Register of Controlled trials (CENTRAL)) from their inception until September 7, 2016. Standardised mean differences (SMDs) were calculated and pooled by means of random effects models. Risk of bias, publication bias and heterogeneity among trials were also assessed. Results Seven studies could be included in the meta-analysis on EC, but only two studies could be included in the meta-analysis on PA (total number of 1440 patients). The results showed no significant differences in EC between HB rehabilitation and UC (SMD 0.10, 95% confidence interval (CI) -0.13 to 0.33). There was a small but significant difference in EC in favour of HB compared to CB rehabilitation (SMD 0.25, 95% CI 0.02-0.48). No differences were found for PA (SMD 0.37, 95% CI -0.18 to 0.92). Conclusions HB exercise is slightly more effective than CB rehabilitation in terms of maintaining EC. The small number of studies warrants the need for more

Reduced bone mass and preserved marrow adipose tissue in patients with inflammatory bowel diseases in long-term remission.

PubMed

Bastos, C M; Araújo, I M; Nogueira-Barbosa, M H; Salmon, C E G; de Paula, F J A; Troncon, L E A

2017-07-01

Bone marrow adipose tissue has not been studied in patients with inactive inflammatory bowel disease. We found that these patients have preserved marrow adiposity even with low bone mass. Factors involved in bone loss in active disease may have long-lasting effects but do not seem to affect bone marrow adiposity. Reduced bone mass is known to occur at varying prevalence in patients with inflammatory bowel diseases (IBD) because of inflammation, malnutrition, and steroid therapy. Osteoporosis may develop in these patients as the result of an imbalanced relationship between osteoblasts and adipocytes in bone marrow. This study aimed to evaluate for the first time bone mass and bone marrow adipose tissue (BMAT) in a particular subgroup of IBD patients characterized by long-term, steroid-free remission. Patients with Crohn's disease (CD; N = 21) and ulcerative colitis (UC; N = 15) and controls (C; N = 65) underwent dual X-ray energy absorptiometry and nuclear magnetic resonance spectroscopy of the L3 lumbar vertebra for BMAT assessment. Both the CD and UC subgroups showed significantly higher proportions of patients than controls with Z-score ≤-2.0 at L1-L4 (C 1.54%; CD 19.05%; UC 20%; p = 0.02), but not at other sites. The proportions of CD patients with a T-score ˂-1.0 at the femoral neck (C 18.46%; CD 47.62%; p = 0.02) and total hip (C 16.92%; CD 42.86%; p = 0.03) were significantly higher than among controls. There were no statistically significant differences between IBD patients and controls regarding BMAT at L3 (C 28.62 ± 8.15%; CD 29.81 ± 6.90%; UC 27.35 ± 9.80%; p = 0.67). IBD patients in long-term, steroid-free remission may have a low bone mass in spite of preserved BMAT. These findings confirm the heterogeneity of bone disorders in IBD and may indicate that factors involved in bone loss in active disease may have long-lasting effects on these patients.

Inflammatory bowel disease in pediatric patients: Characteristics of newly diagnosed patients from the CEDATA-GPGE Registry.

PubMed

Buderus, Stephan; Scholz, Dietmar; Behrens, Rolf; Classen, Martin; De Laffolie, Jan; Keller, Klaus-Michael; Zimmer, Klaus-Peter; Koletzko, Sibylle

2015-02-20

Inflammatory bowel disease (IBD) can arise at any age, with peak incidence in adolescence and young adulthood. A registry of pediatric cases of IBD offers the opportunity to document their diagnosis and treatment, with the ultimate aim of improving diagnosis and treatment in the future. In the German-language CEDATA-GPGE registry, 3991 cases of IBD in patients less than 18 years of age were documented from 2004 to 2014. The 1257 patients who were prospectively included in the registry upon diagnosis and whose further course was documented for at least three months were analyzed in two separate groups--under 10 years old, and 10 years and above--with respect to the type and duration of their symptoms until diagnosis, the completeness of the diagnostic evaluation, the disease phenotype, and the initial treatment. Of the 958 patients for whom full documentation was available, 616 (64.3%) had Crohn's disease (CD), 278 (29%) had ulcerative colitis (UC), 64 (6.7%) had an unclassified IBD, and 23.2% were under 10 years old. The latency to diagnosis was longer for CD than for UC (0.5 versus 0.3 years), regardless of age. 62.5% of the CD patients had ileocolonic involvement, and more than half had involvement of the upper gastrointestinal tract. 71% of the patients with UC had subtotal colitis or pancolitis. Continuous improvement was seen in diagnostic assessment according to published guidelines. For example, in 2004/2005, 69% of patients were evaluated endoscopically with ileocolonoscopy and esophagogastroduodenoscopy; this fraction had risen to nearly 100% by 2013/2014. Similarly, the percentage of patients who underwent a diagnostic evaluation of the small intestine, as recommended, rose from 41.2% to 60.9% over the same period. The most common initial treatments were 5- amino - salicylates (86.8% CD, 100% UC) and glucocorticoids (60.6% CD, 65.6% UC). 32% of the patients with CD received exclusive enteral nutrition therapy. Most of these pediatric patients with IBD

Multi-Center Experience of Vedolizumab Effectiveness in Pediatric Inflammatory Bowel Disease.

PubMed

Singh, Namita; Rabizadeh, Shervin; Jossen, Jacqueline; Pittman, Nanci; Check, Morgan; Hashemi, Ghonche; Phan, Becky L; Hyams, Jeffrey S; Dubinsky, Marla C

2016-09-01

Though vedolizumab has received regulatory approval for the treatment of Crohn's disease (CD) and ulcerative colitis (UC) in adults, there is increasing off-label use in children. To describe the experience with vedolizumab in pediatric inflammatory bowel disease (IBD) patients at 3 tertiary IBD centers and examine predictors of remission. A retrospective review identified pediatric IBD patients (age < 18 yrs) receiving vedolizumab. Data on demographics, disease behavior, location, activity, and previous treatments/surgeries were collected. Disease activity was assessed using the weighted pediatric CD activity index or pediatric UC activity index. Primary outcome was week 14 remission, defined as pediatric UC activity index <10 or weighted pediatric CD activity index <12.5. Descriptive statistics and univariate analyses were performed to examine associations of clinical characteristics with efficacy. Fifty-two patients, 58% CD and 42% UC, initiated vedolizumab between June 2014 and August 2015. Median age at vedolizumab initiation was 14.9 (range 7-17) years. Ninety percent had failed ≥1 anti-tumor necrosis factor (TNF) agent. Week 14 remission rates for UC and CD were 76% and 42%, respectively (P < 0.05). Eighty percent of anti-TNF-naive patients experienced week 14 remission. At week 22, anti-TNF-naive patients had higher remission rates than TNF-exposed patients (100% versus 45%, P = 0.04). There were no infusion reactions or serious adverse events/infections. Our results suggest that vedolizumab is efficacious and safe in pediatric IBD patients, with UC patients experiencing earlier and higher rates of remission than CD patients. Anti-TNF-naive patients experienced higher remission rates than those with anti-TNF exposure. Controlled clinical trial data are needed to confirm these observations.

Risk factors for gallstones and kidney stones in a cohort of patients with inflammatory bowel diseases

PubMed Central

Rossel, Jean-Benoît; Biedermann, Luc; Frei, Pascal; Zeitz, Jonas; Spalinger, Marianne; Battegay, Edouard; Zimmerli, Lukas; Vavricka, Stephan R.; Rogler, Gerhard

2017-01-01

Background Gallstones and kidney stones are known complications of inflammatory bowel diseases (IBD). Risk factors have been insufficiently studied and explanatory studies date back up to 30 years. It remains unclear, whether improved treatment options also influenced risk factors for these complications. Objectives Identifying risk factors for gallstones and kidney stones in IBD patients. Methods Using data from the Swiss Inflammatory Bowel Disease Cohort Study we assessed associations of diseases characteristics with gallstones and kidney stones in univariate and multivariate logistic regression analyses. Results Out of 2323 IBD patients, 104 (7.8%) Crohn’s disease (CD) and 38 (3.8%) ulcerative colitis (UC) patients were diagnosed with gallstones. Significant risk factors for gallstones were diagnosis of CD, age at diagnosis, disease activity and duration, NSAID intake, extra-intestinal manifestations and intestinal surgery. Kidney stones were described in 61 (4.6%) CD and 30 (3.0%) UC patients. Male gender, disease activity, intestinal surgery, NSAID usage and reduced physical activity were significant risk factors. Hospitalization was associated with gallstones and kidney stones. The presence of gallstones increased the risk for kidney stones (OR 4.87, p<0.001). Conclusion The diagnosis of CD, intestinal surgery, prolonged NSAID use, disease activity and duration and bowel stenosis were significantly associated with cholecystonephrolithiasis in IBD. PMID:29023532

Risk factors for gallstones and kidney stones in a cohort of patients with inflammatory bowel diseases.

PubMed

Fagagnini, Stefania; Heinrich, Henriette; Rossel, Jean-Benoît; Biedermann, Luc; Frei, Pascal; Zeitz, Jonas; Spalinger, Marianne; Battegay, Edouard; Zimmerli, Lukas; Vavricka, Stephan R; Rogler, Gerhard; Scharl, Michael; Misselwitz, Benjamin

2017-01-01

Gallstones and kidney stones are known complications of inflammatory bowel diseases (IBD). Risk factors have been insufficiently studied and explanatory studies date back up to 30 years. It remains unclear, whether improved treatment options also influenced risk factors for these complications. Identifying risk factors for gallstones and kidney stones in IBD patients. Using data from the Swiss Inflammatory Bowel Disease Cohort Study we assessed associations of diseases characteristics with gallstones and kidney stones in univariate and multivariate logistic regression analyses. Out of 2323 IBD patients, 104 (7.8%) Crohn's disease (CD) and 38 (3.8%) ulcerative colitis (UC) patients were diagnosed with gallstones. Significant risk factors for gallstones were diagnosis of CD, age at diagnosis, disease activity and duration, NSAID intake, extra-intestinal manifestations and intestinal surgery. Kidney stones were described in 61 (4.6%) CD and 30 (3.0%) UC patients. Male gender, disease activity, intestinal surgery, NSAID usage and reduced physical activity were significant risk factors. Hospitalization was associated with gallstones and kidney stones. The presence of gallstones increased the risk for kidney stones (OR 4.87, p<0.001). The diagnosis of CD, intestinal surgery, prolonged NSAID use, disease activity and duration and bowel stenosis were significantly associated with cholecystonephrolithiasis in IBD.

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.

High-Dose Ursodeoxycholic Acid Is Associated With the Development of Colorectal Neoplasia in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis

PubMed Central

Eaton, John E.; Silveira, Marina G.; Pardi, Darrell S.; Sinakos, Emmanouil; Kowdley, Kris V.; Luketic, Velimir A.C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Lindor, Keith D.

2011-01-01

OBJECTIVES Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28–30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC. METHODS Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer. RESULTS Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30–20.10, P=0.02). CONCLUSIONS Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC. PMID:21556038

Disease outcome of inflammatory bowel disease patients: general outline of a Europe-wide population-based 10-year clinical follow-up study.

PubMed

Wolters, Frank L; Russel, Maurice G; Sijbrandij, Jildou; Schouten, Leo J; Odes, Selwyn; Riis, Lene; Munkholm, Pia; Langholz, Ebbe; Bodini, Paolo; O'Morain, Colm; Katsanos, Kostas; Tsianos, Epameinondas; Vermeire, Severine; Van Zeijl, Gilbert; Limonard, Charles; Hoie, Ole; Vatn, Morten; Moum, Bjørn; Stockbrügger, Reinhold W

2006-01-01

To give a general outline of a 10-year clinical follow-up study of a population-based European cohort of inflammatory bowel disease (IBD) patients and to present the first results in terms of clinical outcome parameters and risk factors. A population-based cohort of newly, prospectively, diagnosed cases was initiated between 1991 and 1993. The 2201 patients with IBD (706 had Crohn's disease (CD), 1379 had ulcerative colitis (UC) and 116 had indeterminate colitis) originated from 20 different areas in 11 different European countries and Israel. For the 10-year follow-up of this cohort, electronic data-collecting instruments were made available through an Internet-based website. Data concerning vital status, disease activity, medication use, surgical events, cancer, pregnancy, fertility, quality of life and health-care costs were gathered. A blood sample was obtained from patients and controls to perform genotypic characterization. Thirteen centres from eight European countries and Israel participated. In 958 (316 CD and 642 UC) out of a total of 1505 IBD patients (64%) from these 13 centres, a complete dataset was obtained at follow-up. Even though an increased mortality risk was observed in CD patients 10 years after diagnosis, a benign disease course was observed in this patient group in terms of disease recurrence. A correlation between ASCA and CARD15 variants in CD patients and complicated disease course was observed. A north-south gradient was observed regarding colectomy rates in UC patients. Direct costs were found to be highest in the first year after diagnosis and greater in CD patients than in UC patients, with marked differences between participating countries. This 10-year clinical follow-up study of a population-based European cohort of IBD patients provides updated information on disease outcome of these patient groups.

VLT near- to mid-IR imaging and spectroscopy of the M 17 UC1 - IRS5 region

NASA Astrophysics Data System (ADS)

Chen, Zhiwei; Nürnberger, Dieter E. A.; Chini, Rolf; Jiang, Zhibo; Fang, Min

2015-06-01

Aims: We investigate the surroundings of the hypercompact H ii region M 17 UC1 to probe the physical properties of the associated young stellar objects and the environment of massive star formation. Methods: We use diffraction-limited near-IR (VLT/NACO) and mid-IR (VLT/VISIR) images to reveal the different morphologies at various wavelengths. Likewise, we investigate the stellar and nebular content of the region with VLT/SINFONI integral field spectroscopy with a resolution R ˜ 1500 at H + K bands. Results: Five of the seven point sources in this region show L-band excess emission. A geometric match is found between the H2 emission and near-IR polarized light in the vicinity of IRS5A, and between the diffuse mid-IR emission and near-IR polarization north of UC1. The H2 emission is typical for dense photodissociation regions (PDRs), which are initially far-ultraviolet pumped and repopulated by collisional de-excitation. The spectral types of IRS5A and B273A are B3-B7 V/III and G4-G5 III, respectively. The observed infrared luminosity LIR in the range 1-20 μm is derived for three objects; we obtain 2.0 × 103 L⊙ for IRS5A, 13 L⊙ for IRS5C, and 10 L⊙ for B273A. Conclusions: IRS5 might be a young quadruple system. Its primary star IRS5A is confirmed to be a high-mass protostellar object (˜9 M⊙, ˜1 × 105 yrs); it might have terminated accretion due to the feedback from stellar activities (radiation pressure, outflow) and the expanding H ii region of M 17. The object UC1 might also have terminated accretion because of the expanding hypercompact H ii region, which it ionizes. The disk clearing process of the low-mass young stellar objects in this region might be accelerated by the expanding H ii region. The outflows driven by UC1 are running south-north with its northeastern side suppressed by the expanding ionization front of M 17; the blue-shifted outflow lobe of IRS5A is seen in two types of tracers along the same line of sight in the form of H2 emission

Partners of patients with ulcerative colitis exhibit a biologically relevant dysbiosis in fecal microbial metacommunities.

PubMed

Chen, Guang-Lan; Zhang, Ye; Wang, Wang-Yue; Ji, Xue-Liang; Meng, Fei; Xu, Pei-Song; Yang, Ning-Min; Ye, Fu-Qiang; Bo, Xiao-Chen

2017-07-07

To investigate alterations in the fecal microbiome using 16S rRNA amplicon sequencing in couples in the same cohabitation environment. Fecal samples were collected from eight ulcerative colitis (UC) patients and their healthy partners at Lishui People's Hospital, Zhejiang Province, China. DNA was extracted and the variable regions V3 and V4 of the 16S rRNA genes were PCR amplified using a two-step protocol. Clear reads were clustered into operational taxonomic units (OTUs) at the 97% sequence similarity level using UCLUST v1.2.22. The Wilcoxon rank-sum test (R v3.1.2) was used to compare inter-individual differences. Differences with a P value < 0.05 were considered statistically significant. Fecal microbial communities were more similar among UC patients than their healthy partners ( P = 0.024). UC individuals had a lower relative abundance of bacteria belonging to the Firmicutes , especially Blautia , Clostridium , Coprococcus and Roseburia ( P < 0.05). Microbiota dysbiosis was detected in UC patients and their healthy partners. Relevant genera included Akkermansiam , Bacteroides , Escherichia , Lactobacillales , Klebsiella and Parabacteroides . The enriched pathways in fecal samples of UC patients were related to lipid and nucleotide metabolism. Additionally, the pathways involved in membrane transport and metabolism of cofactors and vitamins were more abundant in the healthy partners. Our results suggested that the microbial composition might be affected in healthy partners cohabiting with UC patients, especially in terms of microbiota dysbiosis.

Assessment of Atrial Electromechanical Delay and Left Atrial Mechanical Functions in Patients with Ulcerative Colitis.

PubMed

Nar, Gokay; Ergul, Bilal; Aksan, Gokhan; Inci, Sinan

2016-07-01

Ulcerative colitis (UC) is a common inflammatory bowel disease causing systemic inflammation, which may also affect the cardiovascular system, as well as other organ systems. The aim of the current study was to evaluate left atrial (LA) mechanical functions and duration of atrial electromechanical delay (AEMD) with echocardiography in patients with UC. A total of 91 patients, 45 with UC (Group 1) and 46 healthy individuals as control (Group 2) were included in the study. The demographic and laboratory data were recorded, and echocardiographic measurements were taken for all patients. In the evaluation of basal clinical and laboratory findings, no difference was detected between the two groups, except for white blood cell count (WBC) (8.26 ± 2.71 vs. 7.06 ± 1.70, P = 0.013) and high-sensitivity C-reactive protein (Hs-CRP; 3.4 ± 1.7 vs. 1.0 ± 0.8, P < 0.001). The echocardiographic assessment revealed that the diastolic parameters such as E-, E/A-, and E- waves decreased in the UC group when compared to the control group. LA mechanical functions were different between groups, except for left atrial (LA) maximal volume: LA minimum volume (22.2 ± 12.9 vs. 15.3 ± 4.7, P = 0.001), LA volume before atrial systole (29.9 ± 14.2 vs. 24.2 ± 4.9, P = 0.021), LA ejection fraction (27.4 ± 16.5 vs. 38.6 ± 10.1, P < 0.001), LA total emptying volume (17.9 ± 6.9 vs. 21.9 ± 5.9, P = 0.004), LA active emptying fraction (27.4 ± 16.5 vs. 38.6 ± 10.1, P < 0.001), LA active emptying volume (7.7 ± 3.6 vs. 9.4 ± 2.9, P = 0.013), LA passive emptying fraction (26.8 ± 10.2 vs. 33.2 ± 9.2, P = 0.002), and LA passive emptying volume (10.3 ± 4.9 vs. 12.5 ± 4.5, P = 0.029). There was a significant difference between the groups in terms of AEMD durations, except time interval from the onset of the P-wave on the surface ECG to the peak of the late diastolic wave (PA) of the tricuspid valve. The correlation analysis revealed that age and duration of disease were correlated with

A change in temperature modulates defence to yellow (stripe) rust in wheat line UC1041 independently of resistance gene Yr36.

PubMed

Bryant, Ruth R M; McGrann, Graham R D; Mitchell, Alice R; Schoonbeek, Henk-Jan; Boyd, Lesley A; Uauy, Cristobal; Dorling, Steve; Ridout, Christopher J

2014-01-08

Rust diseases are of major importance in wheat production worldwide. With the constant evolution of new rust strains and their adaptation to higher temperatures, consistent and durable disease resistance is a key challenge. Environmental conditions affect resistance gene performance, but the basis for this is poorly understood. Here we show that a change in day temperature affects wheat resistance to Puccinia striiformis f. sp tritici (Pst), the causal agent of yellow (or stripe) rust. Using adult plants of near-isogenic lines UC1041 +/- Yr36, there was no significant difference between Pst percentage uredia coverage in plants grown at day temperatures of 18°C or 25°C in adult UC1041 + Yr36 plants. However, when plants were transferred to the lower day temperature at the time of Pst inoculation, infection increased up to two fold. Interestingly, this response was independent of Yr36, which has previously been reported as a temperature-responsive resistance gene as Pst development in adult UC1041 -Yr36 plants was similarly affected by the plants experiencing a temperature reduction. In addition, UC1041 -Yr36 plants grown at the lower temperature then transferred to the higher temperature were effectively resistant and a temperature change in either direction was shown to affect Pst development up to 8 days prior to inoculation. Results for seedlings were similar, but more variable compared to adult plants. Enhanced resistance to Pst was observed in seedlings of UC1041 and the cultivar Shamrock when transferred to the higher temperature. Resistance was not affected in seedlings of cultivar Solstice by a temperature change in either direction. Yr36 is effective at 18°C, refining the lower range of temperature at which resistance against Pst is conferred compared to previous studies. Results reveal previously uncharacterised defence temperature sensitivity in the UC1041 background which is caused by a change in temperature and independently of Yr36. This novel

The diagnostic value of a new fecal marker, matrix metalloprotease-9, in different types of inflammatory bowel diseases.

PubMed

Farkas, Klaudia; Saródi, Zoltán; Bálint, Anita; Földesi, Imre; Tiszlavicz, László; Szűcs, Mónika; Nyári, Tibor; Tajti, János; Nagy, Ferenc; Szepes, Zoltán; Bor, Renáta; Annaházi, Anita; Róka, Richárd; Molnár, Tamás

2015-03-01

Only limited data are available regarding the diagnostic accuracy of fecal matrix metalloprotease-9 [MMP-9] for inflammatory bowel disease [IBD]. The aims of our study were to assess the diagnostic accuracy of fecal MMP-9 in patients with active Crohn's disease [CD], ulcerative colitis [UC], and pouchitis, and to compare the diagnostic accuracy of fecal MMP-9 and fecal calprotectin [CP] in IBD. Stool and blood samples were collected in 50 CD, 54 UC, and 34 ileal pouch-anal anastomosis patients before control endoscopies were performed. Biopsies were taken for histologic purposes. The activities of CD, UC, and pouchitis were defined with the use of clinical, endoscopic, and histologic activity scores. Fecal CP and MMP-9 levels were quantified by enzyme-linked immunosorbent assay. Active CD, UC, and pouchitis were detected in 38%, 54%, and 29% of the patients, respectively. A significant correlation was revealed between fecal CP and the clinical activities of CD and UC, and between fecal CP and the endoscopic activity of UC and pouchitis. Fecal MMP-9 did not correlate with any of the activity indices of CD; however, strong associations were shown between fecal MMP-9 and clinical, endoscopic, and histologic activities of both UC and pouchitis. This is the first study assessing the diagnostic accuracy of MMP-9 in different types of IBD. Our results showed that fecal MMP-9 has high sensitivity in the detection of endoscopically active UC and pouchitis. These non-invasive methods help assess intestinal inflammation. 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.

Theoretical Model for Volume Fraction of UC, 235U Enrichment, and Effective Density of Final U 10Mo Alloy

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

Devaraj, Arun; Prabhakaran, Ramprashad; Joshi, Vineet V.

2016-04-12

The purpose of this document is to provide a theoretical framework for (1) estimating uranium carbide (UC) volume fraction in a final alloy of uranium with 10 weight percent molybdenum (U-10Mo) as a function of final alloy carbon concentration, and (2) estimating effective 235U enrichment in the U-10Mo matrix after accounting for loss of 235U in forming UC. This report will also serve as a theoretical baseline for effective density of as-cast low-enriched U-10Mo alloy. Therefore, this report will serve as the baseline for quality control of final alloy carbon content

Mucin gene expression in the intestine of ulcerative colitis patients: a systematic review and meta-analysis.

PubMed

Niv, Yaron

2016-11-01

The mucus layer of the colon is the main barrier between luminal microbes and the mucosa, and plays a significant role in the body defense mechanisms. Several studies have examined mucin gene (MUC) expression in ulcerative colitis (UC) without conclusive results. The aim of the study was to establish the knowledge of mucin expression in UC as a basis for further investigation. English medical literature searches were performed for mucin expression in the colonic mucosa of UC patients in comparison with controls. Case-control studies were included. A meta-analysis was carried out using 'Comprehensive meta-analysis' software. Pooled odds ratios (ORs) and 95% confidence intervals were calculated. Altogether, we found 311 eligible studies. Only 10 case-control studies from five countries fulfilled the inclusion criteria. A moderate heterogeneity was found in the studies included: Q=52.703, d.f. (Q)=15.000, I=71.539%. OR for mucin expression in UC patients versus healthy controls was 1.868 with a 95% confidence interval (CI) 1.263-2.764, P=0.002. Thus, we could find a significant increase of 87% of mucin expression in UC patients. OR for MUC2 was 2.520, 95% CI 1.320-4.809, P<0.001. MUC3 was also increased with OR 2.599, 95% CI 1.389-4.861, P=0.003. Funnel plot did not indicate a significant publication bias. We found a global increase in mucin expression in UC patients, specifically in MUC2 and MUC3. Further studies are needed, especially in patients treated with biologics for mucosal healing, to understand the role of mucin expression in the natural history of UC.

Diagnostic Delay in Romanian Patients with Inflammatory Bowel Disease: Risk Factors and Impact on the Disease Course and Need for Surgery

PubMed Central

Zaharie, Roxana; Zaharie, Florin; Tantau, Marcel; Gheorghe, Liana; Gheorghe, Cristian; Gologan, Serban; Cijevschi, Cristina; Trifan, Anca; Dobru, Daniela; Goldis, Adrian; Constantinescu, Gabriel; Iacob, Razvan; Diculescu, Mircea

2016-01-01

Background: The epidemiology of inflammatory bowel disease [IBD] in Eastern Europe is poorly understood, particularly with regard to diagnostic delay. Here we investigated the factors leading to delayed diagnosis and the effect of the delay on several disease progression and outcome measures. Methods: A total of 1196 IBD cases [682 ulcerative colitis [UC], 478 Crohn’s disease [CD], 36 indeterminate colitis] from the Romanian national registry IBDPROSPECT were reviewed. Standard clinical and demographic factors were evaluated as predictors of a long diagnostic delay in both CD and UC. Diagnostic delay was subsequently evaluated as a potential risk factor for bowel stenoses, bowel fistulas, perianal fistulas, perianal surgery, and intestinal surgery in CD patients. Results: The median diagnostic delay was significantly longer in CD [5 months] than in UC [1 month] patients [p < 0.001]. Compared with 5 months for UC patients, 75% of CD patients were diagnosed within 18 months of symptom onset. In CD patients, extra-ileal location was a protective factor (odds ratio [OR], 0.5; p = 0.03), whereas being an active smoker [OR, 2.09; p = 0.01] and symptom onset during summer [OR, 3.35; p < 0.001] were independent risk factors for a long diagnostic delay [> 18 months]. In UC patients, an age > 40 years was a protective factor [OR, 0.68; p = 0.04] for a long delay. Regarding outcomes, a long diagnostic delay in CD patients positively correlated with bowel stenoses [OR, 3.38; p < 0.01] and any IBD-related surgery [OR, 1.95; p = 0.03] and had a positive trend for intestinal fistulas [OR, 2.64; p = 0.08] and perianal fistulas [OR, 2.9; p = 0.07]. Disease duration since diagnosis positively correlated with bowel stenoses [OR, 1.04; p = 0.04], any IBD-related surgery [OR, 1.04; p = 0.02], and intestinal surgery [OR, 1.07; p < 0.01]. Conclusions: A long diagnostic delay in IBD correlates with an increased frequency of bowel stenoses and need for IBD-related surgery. PMID:26589956

Cost-effectiveness of vedolizumab compared with conventional therapy for ulcerative colitis patients in the UK.

PubMed

Wilson, Michele R; Azzabi Zouraq, Ismail; Chevrou-Severac, Helene; Selby, Ross; Kerrigan, Matthew C

2017-01-01

To examine the clinical and economic impact of vedolizumab compared with conventional therapy in the treatment of moderately-to-severely active ulcerative colitis (UC) in the UK based on results of the GEMINI I trial. A decision-analytic model in Microsoft Excel was used to compare vedolizumab with conventional therapy (aminosalicylates, corticosteroids, immunomodulators) for the treatment of patients with UC in the UK. We considered the following three populations: the overall intent-to-treat population from the GEMINI I trial, patients naïve to anti-TNF therapy, and those who had failed anti-TNF-therapy. Population characteristics and efficacy data were obtained from the GEMINI I trial. Other inputs (eg, unit costs, probability of surgery, mortality) were obtained from published literature. Time horizon was a lifetime horizon, with costs and outcomes discounted by 3.5% per year. One-way and probabilistic sensitivity analyses were conducted to measure the impact of parameter uncertainty. Vedolizumab had incremental cost-effectiveness ratios of £4,095/quality-adjusted life-year (QALY), £4,423/QALY, and £5,972/QALY compared with conventional therapy in the intent-to-treat, anti-TNF-naïve, and anti-TNF-failure populations, respectively. Patients on vedolizumab accrued more QALYs while incurring more costs than patients on conventional therapy. The sensitivity analyses showed that the results were most sensitive to induction response and transition probabilities for each treatment. The results suggest that vedolizumab results in more QALYs and may be a cost-effective treatment option compared with conventional therapy for both anti-TNF-naïve and anti-TNF-failure patients with moderately-to-severely active UC.

The impact of Clostridum difficile on surgical rate among ulcerative colitis patients: A systemic review and meta-analysis.

PubMed

Peng, Jiang-Chen; Shen, Jun; Zhu, Qi; Ran, Zhi-Hua

2015-01-01

There is growing recognition of the impact of Clostridum difficile infection (CDI) on patients with inflammatory bowel disease. Clostridium difficile infection causes greater morbidity and mortality. This study aimed to evaluate the impact of C. difficile on surgical risk among ulcerative colitis (UC) patients. We searched the following databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, ACP Journal Club, DARE, CMR, and HTA. Studies were included if fulfilled the following criteria: (1) Cohort or case-control studies, which involved a comparison group that lacked CDI, (2) Patients were given a primary diagnosis of UC, (3) Comorbidity of CDI was evaluated by enzyme immunoassay of stool for C. difficile toxin A and B or C. difficile stool culture, (4) Studies evaluated surgical rate, and (5) Studies reported an estimate of odds ratio, accompanied by a corresponding measure of uncertainty. Five studies with 2380 patients fulfilled the inclusion criteria. Overall, meta-analysis showed that UC with CDI patients had a significant higher surgical rate than patients with UC alone. (OR=1.76, 95% CI=1.36-2.28). C. difficile infection increased the surgical rate in UC patients. However, results should be interpreted with caution, given the limitations of this stud.

PD-1 and PD-L1 inhibitors after platinum-based chemotherapy or in first-line therapy in cisplatin-ineligible patients: Dramatic improvement of prognosis and overall survival after decades of hopelessness in patients with metastatic urothelial cancer.

PubMed

Resch, Irene; Shariat, Shahrokh F; Gust, Kilian M

2018-01-01

Until recently, there were no true innovations in the management of locally advanced (aUC) and metastatic urothelial cancer (mUC) in the last three decades. Vinflunine has been approved by the EMA (European Medicines Agency) with only limited improvement compared to best supportive care in second line treatment. In addition, gemcitabine/cisplatin has been established as an alternative to methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). The advent of checkpoint inhibitors (CPI) revolutionized the care of these patients, transforming a unanimously deadly disease into one with hope through sustained disease control. Five immune CPI have recently been approved for aUC/mUC by the US Food and Drug Administration (FDA) including atezolizumab, nivolumab, pembrolizumab, durvalumab and avelumab. All five CPI are FDA-approved as second-line therapy with atezolizumab and pembrolizumab also being approved for first-line therapy in cisplatin-ineligible patients. The rapid acceptance in the treatment algorithm of UC is based on the impressive clinical efficacy of these agents in some patients, combined with their excellent safety profile. These new agents are indeed the most important advancement in UC care. However, the challenge in the age of precision medicine is to identify the patients who are most likely to benefit from CPIs, as the majority of patients do not respond to CPI. Toward this goal, validation of clinical, molecular and imaging biomarkers that serve for prediction and monitoring of treatment response are of central necessity.

Molecular structure of uranium carbides: Isomers of UC3

NASA Astrophysics Data System (ADS)

Zalazar, M. Fernanda; Rayón, Víctor M.; Largo, Antonio

2013-03-01

In this article, the most relevant isomers of uranium tricarbide are studied through quantum chemical methods. It is found that the most stable isomer has a fan geometry in which the uranium atom is bonded to a quasilinear C3 unit. Both, a rhombic and a ring CU(C2) structures are found about 104-125 kJ/mol higher in energy. Other possible isomers including linear geometries are located even higher. For each structure, we provide predictions for those molecular properties (vibrational frequencies, IR intensities, dipole moments) that could eventually help in their experimental detection. We also discuss the possible routes for the formation of the different UC3 isomers as well as the bonding situation by means of a topological analysis of the electron density.

Molecular structure of uranium carbides: isomers of UC3.

PubMed

Zalazar, M Fernanda; Rayón, Víctor M; Largo, Antonio

2013-03-21

In this article, the most relevant isomers of uranium tricarbide are studied through quantum chemical methods. It is found that the most stable isomer has a fan geometry in which the uranium atom is bonded to a quasilinear C3 unit. Both, a rhombic and a ring CU(C2) structures are found about 104-125 kJ/mol higher in energy. Other possible isomers including linear geometries are located even higher. For each structure, we provide predictions for those molecular properties (vibrational frequencies, IR intensities, dipole moments) that could eventually help in their experimental detection. We also discuss the possible routes for the formation of the different UC3 isomers as well as the bonding situation by means of a topological analysis of the electron density.

CD14+CD33+ myeloid cell-CCL11-eosinophil signature in ulcerative colitis.

PubMed

Lampinen, Maria; Waddell, Amanda; Ahrens, Richard; Carlson, Marie; Hogan, Simon P

2013-11-01

This study tested the hypothesis that eotaxins (CCL11, CCL24, and CCL26) and IL-5 contribute to eosinophil recruitment to the intestine in UC and that intestinal macrophages are important producers of CCL11 in this disease. Peripheral blood and rectal biopsy samples were obtained from patients with active (n=18) and quiescent UC (n=9), and control patients (n=7). Eosinophil and macrophage levels and activation were analyzed by flow cytometry. Rectal mRNA levels of CCL11, CCL24, CCL26, and IL-5 were determined by qRT-PCR. The cellular source of CCL11 was visualized by immunofluorescence analyses. Eosinophil numbers were elevated in the blood and rectum of active and quiescent UC patients compared with controls. Levels of activated eosinophils (CD66b(high)) correlated with disease severity. Rectal CCL11, CCL24, and CCL26 mRNA levels were increased in active UC, whereas only CCL11 was elevated in quiescent UC. Levels of CCL11, but not CCL24 and CCL26, positively correlated with eosinophil numbers. Numbers of CD14(+)CD33(+) cells correlated with CCL11 and eosinophil levels. Immunofluorescence analyses revealed the presence of CD14(+)CCL11(+) mononuclear cells in colonic biopsies in UC. These results support the hypothesis that CCL11 contributes to eosinophil recruitment in UC and that intestinal myeloid cells are a source of CCL11. Interestingly, rectal levels of CCL24, CCL26, and IL-5 only increase during active UC, coinciding with further elevation of eosinophil numbers and with the activation of rectal eosinophils. In conclusion, there is a link among CD14(+)CD33(+) myeloid cells, CCL11, and eosinophils in adult UC.

CD14+CD33+ myeloid cell-CCL11-eosinophil signature in ulcerative colitis

PubMed Central

Lampinen, Maria; Waddell, Amanda; Ahrens, Richard; Carlson, Marie; Hogan, Simon P.

2013-01-01

This study tested the hypothesis that eotaxins (CCL11, CCL24, and CCL26) and IL-5 contribute to eosinophil recruitment to the intestine in UC and that intestinal macrophages are important producers of CCL11 in this disease. Peripheral blood and rectal biopsy samples were obtained from patients with active (n=18) and quiescent UC (n=9), and control patients (n=7). Eosinophil and macrophage levels and activation were analyzed by flow cytometry. Rectal mRNA levels of CCL11, CCL24, CCL26, and IL-5 were determined by qRT-PCR. The cellular source of CCL11 was visualized by immunofluorescence analyses. Eosinophil numbers were elevated in the blood and rectum of active and quiescent UC patients compared with controls. Levels of activated eosinophils (CD66bhigh) correlated with disease severity. Rectal CCL11, CCL24, and CCL26 mRNA levels were increased in active UC, whereas only CCL11 was elevated in quiescent UC. Levels of CCL11, but not CCL24 and CCL26, positively correlated with eosinophil numbers. Numbers of CD14+CD33+ cells correlated with CCL11 and eosinophil levels. Immunofluorescence analyses revealed the presence of CD14+CCL11+ mononuclear cells in colonic biopsies in UC. These results support the hypothesis that CCL11 contributes to eosinophil recruitment in UC and that intestinal myeloid cells are a source of CCL11. Interestingly, rectal levels of CCL24, CCL26, and IL-5 only increase during active UC, coinciding with further elevation of eosinophil numbers and with the activation of rectal eosinophils. In conclusion, there is a link among CD14+CD33+ myeloid cells, CCL11, and eosinophils in adult UC. PMID:23904440

Postoperative Mortality Among Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis of Population-Based Studies.

PubMed

Singh, Sunny; Al-Darmaki, Ahmed; Frolkis, Alexandra D; Seow, Cynthia H; Leung, Yvette; Novak, Kerri L; Ghosh, Subrata; Eksteen, Bertus; Panaccione, Remo; Kaplan, Gilaad G

2015-10-01

There have been varying reports of mortality after intestinal resection for the inflammatory bowel diseases (IBDs). We performed a systematic review and meta-analysis of population-based studies to determine postoperative mortality after intestinal resection in patients with IBD. We searched Medline, EMBASE, and PubMed, from 1990 through 2015, to identify 18 articles and 3 abstracts reporting postoperative mortality among patients with IBD. The studies included 67,057 patients with ulcerative colitis (UC) and 75,971 patients with Crohn's disease (CD), from 15 countries. Mortality estimates stratified by emergent and elective surgeries were pooled separately for CD and UC using a random-effects model. To assess changes over time, the start year of the study was included as a continuous variable in a meta-regression model. In patients with UC, postoperative mortality was significantly lower among patients who underwent elective (0.7%; 95% confidence interval [CI], 0.6%-0.9%) vs emergent surgery (5.3%; 95% CI, 3.8%-7.4%). In patients with CD, postoperative mortality was significantly lower among patients who underwent elective (0.6%; 95% CI, 0.2%-1.7%) vs emergent surgery (3.6%; 95% CI, 1.8%-6.9%). Postoperative mortality did not differ for elective (P = .78) or emergent (P = .31) surgeries when patients with UC were compared with patients with CD. Postoperative mortality decreased significantly over time for patients with CD (P < .05) but not UC (P = .21). Based on a systematic review and meta-analysis, postoperative mortality was high after emergent, but not elective, intestinal resection in patients with UC or CD. Optimization of management strategies and more effective therapies are necessary to avoid emergent surgeries. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Avoiding restorative proctocolectomy for colorectal cancer in patients with ulcerative colitis based on preoperative diagnosis involving p53 immunostaining: report of a case.

PubMed

Sada, Haruki; Shimomura, Manabu; Hinoi, Takao; Egi, Hiroyuki; Kawaguchi, Koji; Yano, Takuya; Niitsu, Hiroaki; Saitou, Yasufumi; Sawada, Hiroyuki; Miguchi, Masashi; Adachi, Tomohiro; Ohdan, Hideki

2015-03-26

The standard operation for colitic cancer in ulcerative colitis (UC) is restorative proctocolectomy; however, sporadic colorectal cancer (CRC) can coincidentally arise in patients with UC and the optimal procedure remains controversial. Therefore, it is crucial to preoperatively determine whether the CRC in UC is a sporadic or colitic cancer. We report a case of avoiding proctocolectomy for sporadic CRC in a patient with UC based on preoperative diagnosis involving p53 immunostaining. A 73-year-old man with CRC in UC had undergone sigmoid colectomy with lymphadenectomy because of the submucosal deep invasion pathologically after endoscopic mucosal resection. The cancer was diagnosed sporadic cancer preoperatively not only based on the endoscopic, clinical, and histological patterns but also that the colon epithelium was unlikely to develop dysplasia as the circumference and unaffected UC mucosa did not detect p53 protein overexpression. Recent reports have shown that the immunohistochemical detection of p53 protein overexpression can be useful for a differential diagnosis and as a predictor of dysplasia and colitic cancer. The analysis of p53 mutation status based on immunostaining of p53 protein expression in the unaffected UC mucosa can be useful for the decision regarding a surgical procedure for CRC in patients with UC.

The course of newly presented unexplained complaints in general practice patients: a prospective cohort study.

PubMed

Koch, H; van Bokhoven, M A; Bindels, P J E; van der Weijden, T; Dinant, G J; ter Riet, G

2009-12-01

Newly presented unexplained complaints (UCs) are common in general practice. Factors influencing the transition of newly presented into persistent UCs have been scarcely investigated. We studied the number and the nature of diagnoses made over time, as well as factors associated with UCs becoming persistent. Finally, we longitudinally studied factors associated with quality of life (QoL). Prospective cohort study in general practice of patients presenting with a new UC. Data sources were case record forms, patient questionnaires and electronic medical registries at inclusion, 1, 6 and 12 months. Presence of complaints and diagnoses made over time were documented. Potential risk factors were assessed in mixed-effect logistic and linear regression models. Sixty-three GPs included 444 patients (73% women; median age 42) with unexplained fatigue (70%), abdominal complaints (14%) and musculoskeletal complaints (16%). At 12 months, 43% of the patients suffered from their initial complaints. Fifty-seven percent of the UCs remained unexplained. UCs had (non-life-threatening) somatic origins in 18% of the patients. QoL was often poor at presentation and tended to remain poor. Being a male [odds ratio (OR) 0.6; 95% confidence interval (CI) 0.4-0.8] and GPs' being more certain about the absence of serious disease (OR 0.9; 95% CI 0.8-0.9) were the strongest predictors of a diminished probability that the complaints would still be present and unexplained after 12 months. The strongest determinants of complaint persistence [regardless of (un)explicability] were duration of complaints >4 weeks before presentation (OR 2.6; 95% CI 1.6-4.3), musculoskeletal complaint at baseline (OR 2.3; 1.2-4.5), while the passage of time acted positively (OR 0.8 per month; 95% CI 0.78-0.84). Musculoskeletal complaints, compared to fatigue, decreased QoL on the physical domain (4.6 points; 2.6-6.7), while presence of psychosocial factors decreased mental QoL (5.0; 3.1-6.9). One year after initial

Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: results from the randomised CORE II study

PubMed Central

Travis, Simon P L; Danese, Silvio; Kupcinskas, Limas; Alexeeva, Olga; D'Haens, Geert; Gibson, Peter R; Moro, Luigi; Jones, Richard; Ballard, E David; Masure, Johan; Rossini, Matteo; Sandborn, William J

2014-01-01

Objective Budesonide MMX is a novel oral formulation of budesonide that uses Multi-Matrix System (MMX) technology to extend release to the colon. This study compared the efficacy of budesonide MMX with placebo in patients with active, mild-to-moderate ulcerative colitis (UC). Design Patients were randomised 1:1:1:1 to receive budesonide MMX 9 mg or 6 mg, or Entocort EC 9 mg (budesonide controlled ileal-release capsules; reference arm) or placebo once daily for 8 weeks. The primary endpoint was combined clinical and endoscopic remission, defined as UC Disease Activity Index score ≤1 with a score of 0 for rectal bleeding and stool frequency, no mucosal friability on colonoscopy, and a ≥1-point reduction in endoscopic index score from baseline. Results 410 patients were evaluated for efficacy. Combined clinical and endoscopic remission rates with budesonide MMX 9 mg or 6 mg, Entocort EC and placebo were 17.4%, 8.3%, 12.6% and 4.5%, respectively. The difference between budesonide MMX 9 mg and placebo was significant (OR 4.49; 95% CI 1.47 to 13.72; p=0.0047). Budesonide MMX 9 mg was associated with numerically higher rates of clinical (42.2% vs 33.7%) and endoscopic improvement (42.2% vs 31.5%) versus placebo. The rate of histological healing (16.5% vs 6.7%; p=0.0361) and proportion of patients with symptom resolution (23.9% vs 11.2%; p=0.0220) were significantly higher for budesonide MMX 9 mg than placebo. Adverse event profiles were similar across groups. Conclusion Budesonide MMX 9 mg was safe and more effective than placebo at inducing combined clinical and endoscopic remission in patients with active, mild-to-moderate UC. PMID:23436336

Effect of Yoga-Based Intervention in Patients with Inflammatory Bowel Disease.

PubMed

Sharma, Purnima; Poojary, Gopal; Dwivedi, Sada Nand; Deepak, Kishore Kumar

2015-01-01

Inflammatory bowel disease (IBD) is a chronic illness characterized by gross inflammation in the gastrointestinal tract that can result in symptoms such as abdominal pain, cramping, diarrhea, and bloody stools. IBD is believed to be influenced by psychological factors such as stress and anxiety. Therefore, a yoga intervention that reduces stress and anxiety may be an effective complementary treatment for these disorders. A total of 100 IBD patients [ulcerative colitis (UC) n = 60 and Crohn's disease (CD) n = 40] during the clinical remission phase of disease were included in the study. These patients were allocated randomly to either the yoga group that underwent an 8-week yoga intervention (physical postures, pranayama, and meditation) 1- hour/day in addition to standard medical therapy (UC, n = 30; CD, n = 20) or the control group (UC, n = 30; CD n = 20), which continued with standard medical therapy alone. The main outcome measures were cardiovascular autonomic functions, serum eosinophilic cationic protein, interleukin- 2 soluble receptors, Speilberger's State Trait Anxiety Inventory (STAI) scores, and clinical symptoms. Before the intervention, all the outcome measures were comparable in the two groups. After the 8-week yoga intervention, fewer UC patients reported arthralgia. The number of patients reporting intestinal colic pain in the control group was higher. State and trait anxiety levels were significantly reduced in patients with UC. However, no significant changes were observed in cardiovascular autonomic functions, eosinophilic cationic proteins, or interleukin-2 soluble receptors. A simplified yoga-based regimen is a safe and effective complementary clinical treatment modality for patients with inflammatory bowel disease during the clinical remission phase.

Monocyte-derived macrophages from Crohn's disease patients are impaired in the ability to control intracellular adherent-invasive Escherichia coli and exhibit disordered cytokine secretion profile.

PubMed

Vazeille, Emilie; Buisson, Anthony; Bringer, Marie-Agnès; Goutte, Marion; Ouchchane, Lemlih; Hugot, Jean-Pierre; de Vallée, Amélie; Barnich, Nicolas; Bommelaer, Gilles; Darfeuille-Michaud, Arlette

2015-05-01

Ileal lesions of Crohn's disease [CD] patients are colonised by adherent-invasive Escherichia coli [AIEC] able to survive in macrophage cell lines. We analysed the ability of monocyte-derived macrophages [MDM] from CD patients to control AIEC intracellular replication and the pro-inflammatory cytokine response of the infected-MDM. Peripheral blood MDM were obtained from 24 CD genotyped for NOD2 and ATG16L1 mutations, 5 ulcerative colitis [UC] patients and 12 healthy controls [HC]. The numbers of intracellular bacteria were determined using gentamicin assay. Cytokine secretion was quantified by ELISA assay. We observed that higher levels of bacteria were internalised within MDM from CD patients than MDM from HC or UC patients. MDM from CD patients were unable to restrict AIEC intracellular replication. Infection of MDM from CD patients with AIEC resulted in significantly increased secretion of IL-6 and tumour necrosis factor alpha [TNF α] than did infection with non-pathogenic E. coli. AIEC-infected MDM from CD patients exhibited a disordered cytokines secretion compared with MDM from UC patients and HC. AIEC-infected MDM from patients with quiescent CD released significantly higher amounts of IL-6 and TNF-alpha than those with active disease or those from HC. The level of secreted TNF-alpha was correlated to the number of intracellular AIEC in MDM from CD patients. Treatment of MDM with infliximab did not change the MDM behaviour. MDM from CD patients are unable to restrict intracellular AIEC replication, leading to disordered inflammatory response influenced by disease activity. 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.

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

The genetic difference between Western and Chinese urothelial cell carcinomas: infrequent FGFR3 mutation in Han Chinese patients.

PubMed

Yuan, Xiaotian; Liu, Cheng; Wang, Kun; Liu, Li; Liu, Tiantian; Ge, Nan; Kong, Feng; Yang, Liu; Björkholm, Magnus; Fan, Yidong; Zhao, Shengtian; Xu, Dawei

2016-05-03

Urothelial cell carcinoma (UCC) includes urothelial bladder carcinoma (UBC), renal pelvic carcinoma (RPC) and ureter carcinoma (UC), and its incidence varies dependent on geographical areas and tumor locations, which indicates different oncogenic mechanisms and/or different genetic susceptibility/environment exposure. The activating mutations of the fibroblast growth factor receptor 3 (FGFR3) gene and telomerase reverse transcriptase (TERT) promoter are the most frequent genetic events in UCCs. These mutations have clinical utilities in UCC initial diagnostics, prognosis, recurrence monitoring and management. However, the vast majority of the results are obtained from studies of UCC patients in Western countries, and little has been known about these in Han Chinese patients. In the present study, we screened the FGFR3 gene and TERT promoter for mutations in 116 UBC, 91 RPC and 115 UC tumors from Han Chinese patients by using Sanger Sequencing. TERT promoter mutations occurred at a high frequency in these UCC patients, comparable with that seen in Western patients, however, the FGFR3 mutation was surprisingly lower, only 9.4% for UBCs, 8.8% for RPCs and 2.6% for UCs, respectively. Taken together, the FGFR3 gene is an infrequent target in the pathogenesis of Han Chinese UCCs, and its mutation detection and targeted therapy have limited clinical utility in these patients. Our results underscore the need for extensive characterization of cancer genomes from diverse patient populations, thereby contributing to precision medicine for cancer treatment and prevention.

Mild-to-moderate ulcerative colitis: your role in patient compliance and health care costs.

PubMed

Tindall, William N; Boltri, John M; Wilhelm, Sheila M

2007-09-01

Ulcerative colitis (UC) is a chronic relapsing disease necessitating lifelong treatment. Most patients present with mild-to-moderate disease characterized by alternating periods of remission and clinical relapse. Continued disease progression and relapse of UC over time are associated with an increased risk of colorectal cancer (CRC). To discuss the latest treatment options for mild-to-moderate UC, to review the current data involving the economics of UC, and to demonstrate the relationship between treatment adherence, clinical relapse, inflammation severity, CRC risk, and treatment outcomes. One of the main goals of therapy in UC is to induce and maintain a long-lasting remission of disease to reduce or avoid the high personal and financial costs of relapse. In recent studies, researchers have demonstrated a link between increased colonic inflammation and CRC risk, highlighting the importance of preventing relapse, which can lead to costly surgical procedures and hospital stays and thus increase the cost of treatment 2- to 20-fold. The risk of disease relapse is affected by several factors, of which the most prominent is nonadherence to maintenance therapy. Nonadherence to therapy can be associated with several other factors, including forgetfulness, male sex, complicated dosing regimens, treatment delivery methods (oral vs. rectal), and pill burden. In the treatment of mild-to-moderate UC, 5-aminosalicyclic acid (5-ASA) is the standard first-line therapy and the treatment of choice for maintaining remission of disease. Novel formulations of 5-ASA and newly devised high-dose 5-ASA regimens offer more options for the treatment of UC and thus may lead to improved treatment adherence, longer remission, and improved patient well-being. Periods of remission during UC treatment must be aggressively maintained to prevent relapse and decrease the risk of an unfavorable outcome. By controlling the risks and conditions that lead to therapeutic nonadherence and relapse among

Ethnic and socio-cultural specificities in Tunisia have no impact on the prevalence of anti-Saccharomyces cerevisiae antibodies in Crohn's disease patients, their relatives or associated clinical factors.

PubMed

Hadrich, Ines; Vandewalle, Peggy; Cheikhrouhou, Fatma; Makni, Fattouma; Krichen, Mohamed Salah; Sendid, Boualem; Standaert-Vitse, Annie; Ayadi, Ali; Poulain, Daniel

2007-06-01

In Western Europe and the USA, the presence of anti-Saccharomyces cerevisiae antibodies (ASCAs) in Crohn's disease (CD) patients and their healthy relatives suggests that ASCAs may be influenced by genetic and/or environmental factors. To assess the prevalence of ASCAs in Tunisian patients with CD or ulcerative colitis (UC), and unaffected family members, in relation to clinical phenotype. Patients and methods. Seventy-seven patients (39 CD, 38 UC), 66 healthy relatives of CD patients, 16 relatives of UC patients and 70 healthy controls were studied. ASCAs were quantified with a new isotype-specific ELISA test involving an antigenic extract from S. cerevisiae strain W303 and by the original test which detects total immunoglobulins against S. cerevisiae Su1 mannan. The specificity of the two tests was identical (91%). The isotype-specific ASCA W303 test was more sensitive than the ASCA Su1 test for immunoglobulin detection, but some CD patients were positive only with this latter test. A high percentage of patients with CD (72%) and their unaffected family members (35%) were ASCA-positive in contrast to UC patients (16%) and their relatives (0%) and controls (8.6%). ASCAs were shown to be independent of rural or urban living, disease activity, but were associated with ileal location. The antigen of S. cerevisiae strain W303 discriminated patients depending on age at onset or location of the disease. This study confirms the antigenic heterogeneity of S. cerevisiae strains in their ability to detect ASCA. It suggests that ASCAs are markers of immunoregulatory disturbance in CD, independently of ethnic/cultural differences between Europe, the USA and North Africa.

Analysis of cytotoxic T lymphocyte associated antigen 4 gene polymorphisms in patients with ulcerative colitis.

PubMed

Lankarani, Kamran B; Karbasi, Ashraf; Kalantari, Tahereh; Yarmohammadi, Hooman; Saberi-Firoozi, Mehdi; Alizadeh-Naeeni, Mahvash; Taghavi, Ali R; Fattahi, Mahammad R; Ghaderi, Abbas

2006-02-01

Ulcerative colitis (UC) is a multifactorial disease associated with dysregulated immunity. Recently, cytotoxic T lymphocyte associated antigen 4 (CTLA-4) gene polymorphisms have been reported in association with several autoimmune diseases in several populations. In the present study, the possible implication of the CTLA-4 gene as a risk factor for UC in the Iranian population was investigated. One hundred UC patients and 100 healthy subjects were studied. CTLA-4 exon 1 position 49 (A/G: codon 17: Thr/Ala) polymorphisms were investigated by polymerase chain reaction single strand confirmation polymorphism method. Four of the patients and one of the healthy controls were excluded from the study because of incomplete DNA extraction. The allele frequencies of A and G in 96 patients (A: 66.1%; G: 33.9%) were not significantly different from the 99 control subjects (A: 63.1%; G: 36.9%, P > 0.05). No significant differences in the distribution of genotype frequencies were observed between A + 49G gene polymorphisms and UC in the Iranian population (P > 0.05). CTLA-4 polymorphism is not associated with UC in the Iranian population.

Online disease management of diabetes: engaging and motivating patients online with enhanced resources-diabetes (EMPOWER-D), a randomized controlled trial.

PubMed

Tang, Paul C; Overhage, J Marc; Chan, Albert Solomon; Brown, Nancy L; Aghighi, Bahar; Entwistle, Martin P; Hui, Siu Lui; Hyde, Shauna M; Klieman, Linda H; Mitchell, Charlotte J; Perkins, Anthony J; Qureshi, Lubna S; Waltimyer, Tanya A; Winters, Leigha J; Young, Charles Y

2013-05-01

To evaluate an online disease management system supporting patients with uncontrolled type 2 diabetes. Engaging and Motivating Patients Online With Enhanced Resources for Diabetes was a 12-month parallel randomized controlled trial of 415 patients with type 2 diabetes with baseline glycosylated hemoglobin (A1C) values ≥7.5% from primary care sites sharing an electronic health record. The intervention included: (1) wirelessly uploaded home glucometer readings with graphical feedback; (2) comprehensive patient-specific diabetes summary status report; (3) nutrition and exercise logs; (4) insulin record; (5) online messaging with the patient's health team; (6) nurse care manager and dietitian providing advice and medication management; and (7) personalized text and video educational 'nuggets' dispensed electronically by the care team. A1C was the primary outcome variable. Compared with usual care (UC, n=189), patients in the intervention (INT, n=193) group had significantly reduced A1C at 6 months (-1.32% INT vs -0.66% UC; p<0.001). At 12 months, the differences were not significant (-1.14% INT vs -0.95% UC; p=0.133). In post hoc analysis, significantly more INT patients had improved diabetes control (>0.5% reduction in A1C) than UC patients at 12 months (69.9 (95% CI 63.2 to 76.5) vs 55.4 (95% CI 48.4 to 62.5); p=0.006). A nurse-led, multidisciplinary health team can manage a population of diabetic patients in an online disease management program. INT patients achieved greater decreases in A1C at 6 months than UC patients, but the differences were not sustained at 12 months. More INT than UC patients achieved improvement in A1C (>0.5% decrease). Trial registered in clinical trials.gov: #NCT00542204.

Online disease management of diabetes: Engaging and Motivating Patients Online With Enhanced Resources-Diabetes (EMPOWER-D), a randomized controlled trial

PubMed Central

Tang, Paul C; Overhage, J Marc; Chan, Albert Solomon; Brown, Nancy L; Aghighi, Bahar; Entwistle, Martin P; Hui, Siu Lui; Hyde, Shauna M; Klieman, Linda H; Mitchell, Charlotte J; Perkins, Anthony J; Qureshi, Lubna S; Waltimyer, Tanya A; Winters, Leigha J; Young, Charles Y

2013-01-01

Objective To evaluate an online disease management system supporting patients with uncontrolled type 2 diabetes. Materials and methods Engaging and Motivating Patients Online With Enhanced Resources for Diabetes was a 12-month parallel randomized controlled trial of 415 patients with type 2 diabetes with baseline glycosylated hemoglobin (A1C) values ≥7.5% from primary care sites sharing an electronic health record. The intervention included: (1) wirelessly uploaded home glucometer readings with graphical feedback; (2) comprehensive patient-specific diabetes summary status report; (3) nutrition and exercise logs; (4) insulin record; (5) online messaging with the patient's health team; (6) nurse care manager and dietitian providing advice and medication management; and (7) personalized text and video educational ‘nuggets’ dispensed electronically by the care team. A1C was the primary outcome variable. Results Compared with usual care (UC, n=189), patients in the intervention (INT, n=193) group had significantly reduced A1C at 6 months (−1.32% INT vs −0.66% UC; p<0.001). At 12 months, the differences were not significant (−1.14% INT vs −0.95% UC; p=0.133). In post hoc analysis, significantly more INT patients had improved diabetes control (>0.5% reduction in A1C) than UC patients at 12 months (69.9 (95% CI 63.2 to 76.5) vs 55.4 (95% CI 48.4 to 62.5); p=0.006). Conclusions A nurse-led, multidisciplinary health team can manage a population of diabetic patients in an online disease management program. INT patients achieved greater decreases in A1C at 6 months than UC patients, but the differences were not sustained at 12 months. More INT than UC patients achieved improvement in A1C (>0.5% decrease). Trial registered in clinical trials.gov: #NCT00542204 PMID:23171659

Decreased colonization of fecal Clostridium coccoides/Eubacterium rectale species from ulcerative colitis patients in an in vitro dynamic gut model with mucin environment.

PubMed

Vermeiren, Joan; Van den Abbeele, Pieter; Laukens, Debby; Vigsnaes, Louise Kristine; De Vos, Martine; Boon, Nico; Van de Wiele, Tom

2012-03-01

The mucus layer in the colon, acting as a barrier to prevent invasion of pathogens, is thinner and discontinuous in patients with ulcerative colitis (UC). A recent developed in vitro dynamic gut model, the M-SHIME, was used to compare long-term colonization of the mucin layer by the microbiota from six healthy volunteers (HV) and six UC patients and thus distinguish the mucin adhered from the luminal microbiota. Although under the same nutritional conditions, short-chain fatty acid production by the luminal communities from UC patients showed a tendency toward a lower butyrate production. A more in-depth community analysis of those microbial groups known to produce butyrate revealed that the diversity of the Clostridium coccoides/Eubacterium rectale and Clostridium leptum group, and counts of Faecalibacterium prausnitzii were lower in the luminal fractions of the UC samples. Counts of Roseburia spp. were lower in the mucosal fractions of the UC samples. qPCR analysis for butyryl-CoA:acetate CoA transferase, responsible for butyrate production, displayed a lower abundance in both the luminal and mucosal fractions of the UC samples. The M-SHIME model revealed depletion in butyrate producing microbial communities not restricted to the luminal but also in the mucosal samples from UC patients compared to HV. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Thrombin generation in mesalazine refractory ulcerative colitis and the influence of low molecular weight heparin.

PubMed

Vrij, Anton A; Oberndorff-Klein-Woolthuis, Ardi; Dijkstra, Gerard; de Jong, Andrea E; Wagenvoord, Rob; Hemker, Hendrik C; Stockbrügger, Reinhold W

2007-10-01

In ulcerative colitis (UC), a state of hypercoagulation has frequently been observed. Low molecular weight heparin (LMWH) has shown beneficial effects as an adjuvant treatment of steroid refractory UC in open trials. We assessed potential therapeutic effects of the LMWH reviparin in hospitalised patients with mesalazine refractory UC, as well as its influence on haemostasis factors. Twenty-nine patients with mild-to-moderately active UC were included in a double-blind placebo controlled trial. All patients had a flare-up of disease under mesalazine treatment. Reviparin (Clivarin) 3,436 IU anti-Xa/0.6 ml or placebo s.c. was added, and self-administered twice daily for 8 weeks. Patients were monitored for possible adverse events and changes in clinical symptoms. Endoscopical, histological, biochemical and haemostasis parameters were analysed. Tolerability and compliance were excellent and no serious adverse events occurred. No significant differences were observed on the clinical, endoscopical and histological outcome, as compared to placebo. A high intrinsic and extrinsic thrombin potential was found before LMWH therapy. However, the significant reduction in the thrombin generation by LMWH was not related to the reduction in disease activity. The LMWH reviparine reduces thrombin generation in patients with mild-to-moderately active, mesalazine refractory UC, but is not associated with a reduction in disease activity.

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.

Ulcerative colitis in a multiracial Asian country: racial differences and clinical presentation among Malaysian patients.

PubMed

Tan, Yan-Mei; Goh, Khean-Lee

2005-10-07

Inflammatory bowel disease appears to be uncommon among Asians. This study was conducted to determine the prevalence of ulcerative colitis (UC) in Malaysian patients and to establish the spectrum of the disease seen in Malaysian patients. Three major Asian races: Malay, Chinese, and Indian co-exist in Malaysia and we sought to determine if there were any racial differences in the prevalence and presentation of disease. Racial differences for several other gastrointestinal diseases have previously been observed and found to be extremely interesting. Data were obtained retrospectively from a review of the medical records of in- and out-patients with a diagnosis of UC at the University Hospital, Kuala Lumpur between 1985 and 1998. There were 45 confirmed cases of UC of which 3 were foreigners, who were excluded from analysis. Thirty new cases of UC were diagnosed during the study period. Their mean age at presentation was 33.0+/-10.0 years. The highest prevalence of UC was 17.9/100 000 hospital admissions in the Indians, followed by 11.2/100 000 hospital admissions in the Chinese. The lowest prevalence was 3.7/100 000 hospital admissions in the Malays. The prevalence of UC was significantly higher in the Indians and the Chinese when compared with the Malays with an OR of 4.89 (CI = 2.02-12.24; chi2 = 15.45, P<0.001) and 3.06 (CI = 1.24-7.78; chi2 = 6.30; P = 0.012) respectively. The extent of colonic disease was similar in the Malay and Indian patients. In contrast, distal or left-sided colitis predominated in the Chinese with an OR of 8.17 (95%CI = 1.31-64.87; chi2 = 5.53, P = 0.02). Extraintestinal manifestations were uncommon (11.9%). UC is an uncommon disease in Malaysia, but racial differences exist. The Indians had the highest prevalence of UC with the Chinese demonstrating the least extensive disease.

Achievement of sustained deep remission with adalimumab in a patient with both refractory ulcerative colitis and seronegative erosive rheumatoid arthritis.

PubMed

Andrisani, G; Gremese, E; Guidi, L; Papa, A; Marzo, M; Felice, C; Pugliese, D; Armuzzi, A

2013-05-27

Inflammatory bowel disease (IBD) is commonly associated with peripheral inflammatory arthritis, and it has been estimated that as many as 12% of IBD patients report these manifestations. However, rheumatoid arthritis (RA) is rarely associated with ulcerative colitis (UC). Among all the biological agents available, nine have been currently approved for the treatment of RA. Conversely, only Infliximab and recently Adalimumab have been approved for UC. In particular, the efficacy of Adalimumab in UC has been demonstrated by both recent randomized controlled trials and real-life studies. Moreover, Adalimumab is a well-established treatment for RA. Herein, we describe a patient with RA and UC treated successfully with ADA.

Patient considerations in the management of ulcerative colitis – role of vedolizumab

PubMed Central

Kothari, Megha; Mudireddy, Prashant; Swaminath, Arun

2015-01-01

Ulcerative colitis (UC) is a subtype of inflammatory bowel disease which causes inflammation of the large intestine and affects approximately 7.6–24.6 per 100,000 persons. The therapeutic goal for UC patients is inducing remission, maintaining remission, and ideally, obtaining mucosal healing. Vedolizumab, approved by the US Food and Drug Administration in May 2014 for the treatment of moderate-to-severe UC and Crohn’s disease, is a newly developed anti-integrin therapy. This review focuses on the preclinical development of vedolizumab and data from early trials, and details the results of the landmark trails that led to its approval in the USA with a specific focus on the management of UC. Additionally, data on safety and the current UC management protocols are also discussed. PMID:26316768

Follow the Money: Engineering at Stanford and UC Berkeley during the Rise of Silicon Valley

ERIC Educational Resources Information Center

Adams, Stephen B.

2009-01-01

A comparison of the engineering schools at UC Berkeley and Stanford during the 1940s and 1950s shows that having an excellent academic program is necessary but not sufficient to make a university entrepreneurial (an engine of economic development). Key factors that made Stanford more entrepreneurial than Cal during this period were superior…

Strategies in maintenance for patients receiving long-term therapy (SIMPLE): a study of MMX mesalamine for the long-term maintenance of quiescent ulcerative colitis.

PubMed

Kane, Sunanda; Katz, Seymour; Jamal, M Mazen; Safdi, Michael; Dolin, Ben; Solomon, Dory; Palmen, Mary; Barrett, Karen

2012-06-01

This was a phase IV, multicenter, open-label, 12-14-month study to assess clinical recurrence in patients with ulcerative colitis (UC) who received maintenance treatment with MMX Multi Matrix System (MMX) mesalamine. A secondary outcome was the relationship between long-term efficacy and adherence. Patients with quiescent UC (no rectal bleeding; 0-1 bowel movements more than normal per day) were enrolled directly into a 12-month maintenance phase of the study during which they received MMX mesalamine 2.4 g/day given once daily (QD). Patients with active, mild-to-moderate UC at screening were enrolled into a 2-month acute phase; those who achieved quiescence could continue into the maintenance phase. The primary endpoint was clinical recurrence at Month 6. Of the 290 patients enrolled, 208 entered the maintenance phase; 152 directly and 56 via the acute phase. Following 6 and 12 months of treatment, 76.5% and 64.4% of evaluable patients, respectively, were recurrence-free. The majority of evaluable patients at Month 6 (81.6%) and Month 12 (79.4%) in the maintenance phase were ≥ 80% adherent to MMX mesalamine. At Month 6, clinical recurrence was observed in 20.6% of patients who were ≥ 80% adherent and 36.1% of patients with <80% adherence (P = 0.05 [post-hoc chi-square analysis]); 31.2% and 52.5% at Month 12 (P = 0.01 [post-hoc chi-square analysis]). MMX mesalamine 2.4 g/day QD is effective for maintaining quiescence in patients with UC. Furthermore, adherence to prescribed treatment yielded lower rates of clinical recurrence. Continued education regarding the importance of long-term 5-aminosalicylic acid therapy is warranted. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

New serological markers in pediatric patients with inflammatory bowel disease

PubMed Central

Kovács, Márta; Müller, Katalin Eszter; Papp, Mária; Lakatos, Péter László; Csöndes, Mihály; Veres, Gábor

2014-01-01

The spectrum of serological markers associated with inflammatory bowel disease (IBD) is rapidly growing. Due to frequently delayed or missed diagnoses, the application of non-invasive diagnostic tests for IBD, as well as differentiation between ulcerative colitis (UC) and Crohn’s disease (CD), would be useful in the pediatric population. In addition, the combination of pancreatic autoantibodies and antibodies against Saccharomyces cerevisiae antibodies/perinuclear cytoplasmic antibody (pANCA) improved the sensitivity of serological markers in pediatric patients with CD and UC. Some studies suggested that age-associated differences in the patterns of antibodies may be present, particularly in the youngest children. In CD, most patients develop stricturing or perforating complications, and a significant number of patients undergo surgery during the disease course. Based on recent knowledge, serum antibodies are qualitatively and quantitatively associated with complicated CD behavior and CD-related surgery. Pediatric UC is characterized by extensive colitis and a high rate of colectomy. In patients with UC, high levels of anti-CBir1 and pANCA are associated with the development of pouchitis after ileal pouch-anal anastomosis. Thus, serologic markers for IBD can be applied to stratify IBD patients into more homogeneous subgroups with respect to disease progression. In conclusion, identification of patients at an increased risk of rapid disease progression is of great interest, as the application of early and more aggressive pharmaceutical intervention could have the potential to alter the natural history of IBD, and reduce complications and hospitalizations. PMID:24803798

Recent trends and future directions for the medical treatment of ulcerative colitis.

PubMed

Naganuma, Makoto; Mizuno, Shinta; Nanki, Kosaku; Sugimoto, Shinya; Kanai, Takanori

2016-12-01

Recently, several medical treatments for ulcerative colitis (UC) have been developed, including 5-aminosalicylic acids (5-ASAs), corticosteroids, thiopurine, calcineurin inhibitors, and anti-tumor necrosis factor (TNF) α treatments. Treatment options including calcineurin inhibitors and anti-TNF treatment for refractory UC are discussed in this article. Furthermore, upcoming treatments are introduced, such as golimumab, vedolizumab, AJM300, tofacitinib. Budesonide foamwill be used as one treatment option in patients with distal colitis. Herbal medicine, such as Qing-Dai is also effective for active UC and may be useful for patients who are refractory to anti-TNFα treatments. In the near future, physicians will able to use many different treatments for UC patients. However, we should not forget 5-ASA and corticosteroids as the fundamental treatments for UC patients.

Effectiveness and Safety of Vedolizumab in Anti-TNF-Naïve Patients With Inflammatory Bowel Disease-A Multicenter Retrospective European Study.

PubMed

Kopylov, Uri; Verstockt, Bram; Biedermann, Luc; Sebastian, Shaji; Pugliese, Daniela; Sonnenberg, Elena; Steinhagen, Peter; Arebi, Naila; Ron, Yulia; Kucharzik, Torsten; Roblin, Xavier; Ungar, Bella; Shitrit, Ariella Bar-Gil; Ardizzone, Sandro; Molander, Pauliina; Coletta, Marina; Peyrin-Biroulet, Laurent; Bossuyt, Peter; Avni-Biron, Irit; Tsoukali, Emmanouela; Allocca, Mariangela; Katsanos, Konstantinos; Raine, Tim; Sipponen, Taina; Fiorino, Gionata; Ben-Horin, Shomron; Eliakim, Rami; Armuzzi, Alessandro; Siegmund, Britta; Baumgart, Daniel C; Kamperidis, Nikolaos; Maharshak, Nitsan; Maaser, Christian; Mantzaris, Gerassimos; Yanai, Henit; Christodoulou, Dimitrious K; Dotan, Iris; Ferrante, Marc

2018-05-18

Vedolizumab (VDZ) is effective for treatment of ulcerative colitis (UC) and Crohn's disease (CD). In GEMINI trials, anti-tumor necrosis factor (anti-TNF)-naïve patients had a superior response compared with anti-TNF-exposed patients. In real-world experience (RWE), the number of included anti-TNF-naïve patients was low. We aimed to evaluate the effectiveness and safety of VDZ in anti-TNF-naïve patients in an RWE setting. This retrospective multicenter European pooled cohort study included consecutive active anti-TNF-naïve IBD patients treated with VDZ. The primary end point was clinical response at week 14. Patients with follow-up beyond week 14 and those discontinuing VDZ at any time were included for maintenance outcomes analysis. Since January 2015, 184 anti-TNF-naïve patients from 23 centers initiated VDZ treatment (Crohn's disease [CD], 50; ulcerative colitis [UC], 134). In CD, 42/50 (82%) patients responded by week 14 and 32 (64%) were in clinical remission; 26/50 (52%) achieved corticosteroid-free remission (CSFR). At last follow-up (44 weeks; interquartile range [IQR], 30-52 weeks), 27/35 (77.1%) patients with available data responded to treatment; 24/35 (68.6%) were in clinical remission, 21/35 (60%) were in CSFR. For UC, 116/134 (79.1%) responded to treatment by week 14, including 53 (39.5%) in clinical remission; 49/134 (36.6%) achieved CSFR. At last follow-up (42.5 weeks; IQR, 30-52 weeks), 79/103 (76.7%) patients responded to treatment, 69/103 (67.0%) were in remission, and 61/103 (59.2%) were in CSFR. Adverse effects were reported in 20 (11%) of the patients, leading to treatment discontinuation in 6 (3.3%). VDZ is similarly effective in ant-TNF-naïve CD and UC patients. The efficacy is higher than reported in anti-TNF-experienced patients and is comparable to that of anti-TNF biologics in this population.

Estimation of quality of life in Cypriot patients with inflammatory bowel disease.

PubMed

Tsoukka, Maria; Jelastopulu, Eleni; Lavranos, Giagkos; Charalambous, George

2017-01-07

To investigate the health-related quality of life (HRQoL) of patients suffering with idiopathic inflammatory bowel disease (IBD). The Greek validated version of the Short Inflammatory Bowel Disease Questionnaire was used for evaluating the quality of life of IBD patients. The questionnaire was distributed to 100 consecutive patients suffering from IBD and presenting for a clinic appointment at the endoscopy unit of Larnaca General Hospital during the period from October to November 2012. The criteria for participating in this study were constituted by the documented diagnosis of either ulcerative colitis (UC) or Crohn's disease (CD) after endoscopy and histologic examination at least 6 months before the study, adult patients (18 years old or older), the capability of verbal communication and the patient's written consent for attending this study. The majority of the questionnaires were completed by a nurse practitioner who specializes in IBD patient care. Regarding the physical dimension in patients with UC, males scored significantly higher than females (4.2 vs 3.4, P = 0.023). Higher scores were also observed in UC patients younger than 35 or older than 50 years (4.0 and 4.2 vs 3.2, respectively, P = 0.021). The psychological dimension revealed similar results in patients with UC, with males, and older ages scoring higher (5.0 vs 3.0, P = 0.01 and 4.7 vs 2.7, P < 0.5, respectively), whereas regarding CD higher scores were observed in married compared to unmarried (3.83 vs 2.33, P = 0.042). No statistical differences in any parameters in the social dimension were observed. Regarding the treatment of, patients with CD, overall higher scores were observed when treated with biological factors compared to standard therapy in all dimensions but with statistical significant difference in the social dimension (5.00 vs 3.25, P = 0.045). The study reveals a negative impact of IBD on HRQoL. Increased risks are age and gender in patients with UC and family status in patients

A Novel Model for Predicting Incident Moderate to Severe Anemia and Iron Deficiency in Patients with Newly Diagnosed Ulcerative Colitis.

PubMed

Khan, Nabeel; Patel, Dhruvan; Shah, Yash; Yang, Yu-Xiao

2017-05-01

Anemia and iron deficiency are common complications of ulcerative colitis (UC). We aimed to develop and internally validate a prediction model for the incidence of moderate to severe anemia and iron deficiency anemia (IDA) in newly diagnosed patients with UC. Multivariable logistic regression was performed among a nationwide cohort of patients who were newly diagnosed with UC in the VA health-care system. Model development was performed in a random two-third of the total cohort and then validated in the remaining one-third of the cohort. As candidate predictors, we examined routinely available data at the time of UC diagnosis including demographics, medications, laboratory results, and endoscopy findings. A total of 789 patients met the inclusion criteria. For the outcome of moderate to severe anemia, age, albumin level and mild anemia at UC diagnosis were predictors selected for the model. The AUC for this model was 0.69 (95% CI 0.64-0.74). For the outcome of moderate to severe anemia with evidence of iron deficiency, the predictors included African-American ethnicity, mild anemia, age, and albumin level at UC diagnosis. The AUC was 0.76, (95% CI 0.69-0.82). Calibration was consistently good in all models (Hosmer-Lemeshow goodness of fit p > 0.05). The models performed similarly in the internal validation cohort. We developed and internally validated a prognostic model for predicting the risk of moderate to severe anemia and IDA among newly diagnosed patients with UC. This will help identify patients at high risk of these complications, who could benefit from surveillance and preventive measures.

Compassionate access anti-tumour necrosis factor-α therapy for ulcerative colitis in Australia: the benefits to patients.

PubMed

Costello, S P; Ghaly, S; Beswick, L; Pudipeddi, A; Agarwal, A; Sechi, A; O'Connor, S; Connor, S J; Sparrow, M P; Bampton, P; Walsh, A J; Andrews, J M

2015-06-01

The efficacy of infliximab has been demonstrated in patients with both acute severe and moderate-severe ulcerative colitis (UC). However, there is a need for 'real-life data' to ensure that conclusions from trial settings are applicable in usual care. We therefore examined the national experience of anti-tumour necrosis factor-α (TNF-α) therapy in UC. Case notes review of patients with UC who had received compassionate access (CA) anti-TNF-α therapy from prospectively maintained inflammatory bowel disease databases of six Australian adult teaching hospitals. Patients either received drug for acute severe UC (ASUC) failing steroids (n = 29) or for medically refractory UC (MRUC) (n = 35). In ASUC, the treating physicians judged that anti-TNF-α therapy was successful in 20/29 patients (69%); in these cases, anti-TNF-α was able to be discontinued (after 1-3 infusions in 19/20 responders) as clinical remission was achieved. Consistent with this perceived benefit, only 7/29 (24%) subsequently underwent colectomy during a median follow up of 12 months (interquartile range (IQR) 5-16). Eight of the 35 patients with MRUC (23%) required colectomy during a median follow up of 28 months (IQR 11-43). The majority of these patients (20/35 or 57%) had anti-TNF-α therapy for ≥4 months, whereas, 27/29 (93%) of ASUC patients had CA for ≤3 months. These data show an excellent overall benefit for anti-TNF-α therapy in both ASUC and MRUC. In particular, only short-duration anti-TNF-α was required in ASUC. These real-life data thus support the clinical trial data and should lead to broader use of this therapy in UC. © 2015 Royal Australasian College of Physicians.

Increased cholestatic enzymes in two patients with long-term history of ulcerative colitis: consider primary biliary cholangitis not always primary sclerosing cholangitis.

PubMed

Polychronopoulou, Erietta; Lygoura, Vasiliki; Gatselis, Nikolaos K; Dalekos, George N

2017-09-25

Several hepatobiliary disorders have been reported in ulcerative colitis (UC) patients with primary sclerosing cholangitis (PSC) being the most specific. Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, rarely occurs in UC. We present two PBC cases of 67 and 71 years who suffered from long-standing UC. Both patients were asymptomatic but they had increased cholestatic enzymes and high titres of antimitochondrial antibodies (AMA)-the laboratory hallmark of PBC. After careful exclusion of other causes of cholestasis by MRI/magnetic resonance cholangiopancreatography (MRCP), virological and microbiological investigations, a diagnosis of PBC associated with UC was established. The patients started ursodeoxycholic acid (13 mg/kg/day) with complete response. During follow-up, both patients remained asymptomatic with normal blood biochemistry. Although PSC is the most common hepatobiliary manifestation among patients with UC, physicians must keep also PBC in mind in those with unexplained cholestasis and repeatedly normal MRCP. In these cases, a reliable AMA testing can help for an accurate diagnosis. © 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.

Cloning and Characterization of the Pyrrolomycin Biosynthetic Gene Clusters from Actinosporangium vitaminophilum ATCC 31673 and Streptomyces sp. Strain UC 11065▿

PubMed Central

Zhang, Xiujun; Parry, Ronald J.

2007-01-01

The pyrrolomycins are a family of polyketide antibiotics, some of which contain a nitro group. To gain insight into the nitration mechanism associated with the formation of these antibiotics, the pyrrolomycin biosynthetic gene cluster from Actinosporangium vitaminophilum was cloned. Sequencing of ca. 56 kb of A. vitaminophilum DNA revealed 35 open reading frames (ORFs). Sequence analysis revealed a clear relationship between some of these ORFs and the biosynthetic gene cluster for pyoluteorin, a structurally related antibiotic. Since a gene transfer system could not be devised for A. vitaminophilum, additional proof for the identity of the cloned gene cluster was sought by cloning the pyrrolomycin gene cluster from Streptomyces sp. strain UC 11065, a transformable pyrrolomycin producer. Sequencing of ca. 26 kb of UC 11065 DNA revealed the presence of 17 ORFs, 15 of which exhibit strong similarity to ORFs in the A. vitaminophilum cluster as well as a nearly identical organization. Single-crossover disruption of two genes in the UC 11065 cluster abolished pyrrolomycin production in both cases. These results confirm that the genetic locus cloned from UC 11065 is essential for pyrrolomycin production, and they also confirm that the highly similar locus in A. vitaminophilum encodes pyrrolomycin biosynthetic genes. Sequence analysis revealed that both clusters contain genes encoding the two components of an assimilatory nitrate reductase. This finding suggests that nitrite is required for the formation of the nitrated pyrrolomycins. However, sequence analysis did not provide additional insights into the nitration process, suggesting the operation of a novel nitration mechanism. PMID:17158935

Umbilical cord-derived mesenchymal stem cells reversed the suppressive deficiency of T regulatory cells from peripheral blood of patients with multiple sclerosis in a co-culture – a preliminary study

PubMed Central

Yang, Hongna; Sun, Jinhua; Wang, Feng; Li, Yan; Bi, Jianzhong; Qu, Tingyu

2016-01-01

The immunoregulatory function of T regulatory cells (Tregs) is impaired in multiple sclerosis (MS). Recent studies have shown that umbilical cord-derived mesenchymal stem cells (UC-MSCs) exert regulatory effect on the functions of immune cells. Thus, we investigated whether UC-MSCs could improve the impaired function of Tregs from MS patients. Co-cultures of UC-MSCs with PBMCs of MS patients were performed for 3 days. Flow cytometry was used to determine the frequency of Tregs. A cell proliferation assay was used to evaluate the suppressive capacity of Tregs. ELISA was conducted for cytokine analysis in the co-cultures. Our results showed that UC-MSCs significantly increased the frequency of CD4+CD25+CD127low/− Tregs in resting CD4+ T cells (p<0.01) from MS, accompanied by the significantly augmented production of cytokine prostaglandin E2, transforming growth factor (−β1, and interleukin-10, along with a reduced interferon-γ production in these co-cultures (p<0.05 - 0.01). More importantly, UC-MSC-primed Tregs of MS patients significantly inhibited the proliferation of PHA-stimulated autologous and allogeneic CD4+CD25− T effector cells (Teffs) from MS patients and healthy individuals compared to non-UC-MSC-primed (naïve) Tregs from the same MS patients (p<0.01). Furthermore, no remarkable differences in suppressing the proliferation of PHA-stimulated CD4+CD25− Teffs was observed in UC-MSC-primed Tregs from MS patients and naïve Tregs from healthy subjects. The impaired suppressive function of Tregs from MS can be completely reversed in a co-culture by UC-MSC modulation. This report is the first to demonstrate that functional defects of Tregs in MS can be repaired in vitro using a simple UC-MSC priming approach. PMID:27705922

Inflammatory bowel disease: A descriptive study of 716 local Chilean patients

PubMed Central

Simian, Daniela; Fluxá, Daniela; Flores, Lilian; Lubascher, Jaime; Ibáñez, Patricio; Figueroa, Carolina; Kronberg, Udo; Acuña, Raúl; Moreno, Mauricio; Quera, Rodrigo

2016-01-01

AIM: To demographically and clinically characterize inflammatory bowel disease (IBD) from the local registry and update data previously published by our group. METHODS: A descriptive study of a cohort based on a registry of patients aged 15 years or older who were diagnosed with IBD and attended the IBD program at Clínica Las Condes in Santiago, Chile. The registry was created in April 2012 and includes patients registered up to October 2015. The information was anonymously downloaded in a monthly report, and the information on patients with more than one visit was updated. The registry includes demographic, clinical and disease characteristics, including the Montreal Classification, medical treatment, surgeries and hospitalizations for crisis. Data regarding infection with Clostridium difficile (C. difficile) were incorporated in the registry in 2014. Data for patients who received consultations as second opinions and continued treatment at this institution were also analyzed. RESULTS: The study included 716 patients with IBD: 508 patients (71%) were diagnosed with ulcerative colitis (UC), 196 patients (27%) were diagnosed with Crohn’s disease (CD) and 12 patients (2%) were diagnosed with unclassifiable IBD. The UC/CD ratio was 2.6/1. The median age was 36 years (range 16-88), and 58% of the patients were female, with a median age at diagnosis of 29 years (range 5-76). In the past 15 years, a sustained increase in the number of patients diagnosed with IBD was observed, where 87% of the patients were diagnosed between the years 2001 and 2015. In the cohort examined in the present study, extensive colitis (50%) and colonic involvement (44%) predominated in the patients with UC and CD, respectively. In CD patients, non-stricturing/non-penetrating behavior was more frequent (80%), and perianal disease was observed in 28% of the patients. There were significant differences in treatment between UC and CD, with a higher use of corticosteroids, and immunosuppressive

Efficacy and Safety of Adalimumab in Moderately to Severely Active Cases of Ulcerative Colitis: A Meta-Analysis of Published Placebo-Controlled Trials

PubMed Central

Zhang, Zong Mei; Li, Wei; Jiang, Xue Liang

2016-01-01

Background/Aims To evaluate the efficacy and safety of adalimumab (ADA) in moderately to severely active ulcerative colitis (UC) patients who are unresponsive to traditional therapy. Methods Electronic databases, including the PubMed, Embase, and Cochrane databases, were searched to April 20, 2014. UC-related randomized controlled trials (RCTs) that compared ADA with placebo were eligible. Review Manager 5.1 was used for data analysis. Results This meta-analysis included three RCTs. ADA was considerably more effective compared with a placebo, and it increased the ratio of patients with clinical remission, clinical responses, mucosal healing and inflammatory bowel disease questionnaire responses in the induction and maintenance phases (p<0.05), as well as patients with steroid-free remission (p<0.05) during the maintenance phase. Clinical remission was achieved in a greater number of UC cases in the ADA 160/80/40 mg groups (0/2/4 week, every other week) compared with the placebo group at week 8 (p=0.006) and week 52 (p=0.0002), whereas the week 8 clinical remission rate was equivalent between the ADA 80/40 mg groups and the placebo group. Among the patients who received immunomodulators (IMM) at baseline, ADA was superior to the placebo in terms of inducing clinical remission (p=0.01). Between-group differences were not observed in terms of serious adverse events (p=0.61). Conclusions ADA, particularly at doses of 160/80/40 mg (0/2/4 week, every other week), is effective and safe in patients with moderate-to-severe UC who are unresponsive to traditional treatment. Concomitant IMM therapy may improve the short-term therapeutic efficacy of ADA. PMID:26780088

Efficacy and Safety of Adalimumab in Moderately to Severely Active Cases of Ulcerative Colitis: A Meta-Analysis of Published Placebo-Controlled Trials.

PubMed

Zhang, Zong Mei; Li, Wei; Jiang, Xue Liang

2016-03-01

To evaluate the efficacy and safety of adalimumab (ADA) in moderately to severely active ulcerative colitis (UC) patients who are unresponsive to traditional therapy. Electronic databases, including the PubMed, Embase, and Cochrane databases, were searched to April 20, 2014. UC-related randomized controlled trials (RCTs) that compared ADA with placebo were eligible. Review Manager 5.1 was used for data analysis. This meta-analysis included three RCTs. ADA was considerably more effective compared with a placebo, and it increased the ratio of patients with clinical remission, clinical responses, mucosal healing and inflammatory bowel disease questionnaire responses in the induction and maintenance phases (p<0.05), as well as patients with steroid-free remission (p<0.05) during the maintenance phase. Clinical remission was achieved in a greater number of UC cases in the ADA 160/80/40 mg groups (0/2/4 week, every other week) compared with the placebo group at week 8 (p=0.006) and week 52 (p=0.0002), whereas the week 8 clinical remission rate was equivalent between the ADA 80/40 mg groups and the placebo group. Among the patients who received immunomodulators (IMM) at baseline, ADA was superior to the placebo in terms of inducing clinical remission (p=0.01). Between-group differences were not observed in terms of serious adverse events (p=0.61). ADA, particularly at doses of 160/80/40 mg (0/2/4 week, every other week), is effective and safe in patients with moderate-to-severe UC who are unresponsive to traditional treatment. Concomitant IMM therapy may improve the short-term therapeutic efficacy of ADA.

Effect of probiotics on inducing remission and maintaining therapy in ulcerative colitis, Crohn's disease, and pouchitis: meta-analysis of randomized controlled trials.

PubMed

Shen, Jun; Zuo, Zhi-Xiang; Mao, Ai-Ping

2014-01-01

Whether probiotics are beneficial at all stages of treatment in inflammatory bowel disease or superior to placebo remains controversial. Two reviewers independently selected randomized controlled trials comparing probiotics with controls in inflammatory bowel disease and extracted data related to remission/response rates, relapse rates, and adverse events. Subanalyses were also performed. Twenty-three randomized controlled trials with a total of 1763 participants met the inclusion criteria. From the meta-analysis, probiotics significantly increase the remission rates in patients with active ulcerative colitis (UC) (P = 0.01, risk ratio [RR] = 1.51). The remission rates were significantly higher in patients with active UC treated with probiotics than placebo (P < 0.0001, RR = 1.80). Unfortunately, subgroup analysis found that only VSL#3 significantly increased the remission rates compared with controls in patients with active UC (P = 0.004, RR = 1.74). Interestingly, VSL#3 (P < 0.00001, RR = 0.18) also significantly reduced the clinical relapse rates for maintaining remission in patients with pouchitis. No significantly different adverse events were detected between probiotics and controls in the treatment of UC (P = 0.94, RR = 0.99) or CD (P = 0.33, RR = 0.87). Administration of probiotics results in additional benefit in inducing remission of patients with UC. VSL#3 are beneficial for maintaining remission in patients with pouchitis. And, probiotics can provide the similar effect as 5-aminosalicylic acid on maintaining remission of UC, although no additional adverse events presented.

Systematic analysis of factors associated with progression and regression of ulcerative colitis in 918 patients.

PubMed

Safroneeva, E; Vavricka, S; Fournier, N; Seibold, F; Mottet, C; Nydegger, A; Ezri, J; Straumann, A; Rogler, G; Schoepfer, A M

2015-09-01

Studies that systematically assess change in ulcerative colitis (UC) extent over time in adult patients are scarce. To assess changes in disease extent over time and to evaluate clinical parameters associated with this change. Data from the Swiss IBD cohort study were analysed. We used logistic regression modelling to identify factors associated with a change in disease extent. A total of 918 UC patients (45.3% females) were included. At diagnosis, UC patients presented with the following disease extent: proctitis [199 patients (21.7%)], left-sided colitis [338 patients (36.8%)] and extensive colitis/pancolitis [381 (41.5%)]. During a median disease duration of 9 [4-16] years, progression and regression was documented in 145 patients (15.8%) and 149 patients (16.2%) respectively. In addition, 624 patients (68.0%) had a stable disease extent. The following factors were identified to be associated with disease progression: treatment with systemic glucocorticoids [odds ratio (OR) 1.704, P = 0.025] and calcineurin inhibitors (OR: 2.716, P = 0.005). No specific factors were found to be associated with disease regression. Over a median disease duration of 9 [4-16] years, about two-thirds of UC patients maintained the initial disease extent; the remaining one-third had experienced either progression or regression of the disease extent. © 2015 John Wiley & Sons Ltd.

Using optical markers of nondysplastic rectal epithelial cells to identify patients with ulcerative colitis-associated neoplasia.

PubMed

Bista, Rajan K; Brentnall, Teresa A; Bronner, Mary P; Langmead, Christopher J; Brand, Randall E; Liu, Yang

2011-12-01

Current surveillance guidelines for patients with long-standing ulcerative colitis (UC) recommend repeated colonoscopy with random biopsies, which is time-consuming, discomforting, and expensive. A less invasive strategy is to identify neoplasia by analyzing biomarkers from the more accessible rectum to predict the need for a full colonoscopy. The goal of this pilot study was to evaluate whether optical markers of rectal mucosa derived from a novel optical technique, partial-wave spectroscopic microscopy (PWS), could identify UC patients with high-grade dysplasia (HGD) or cancer (CA) present anywhere in their colon. Banked frozen nondysplastic mucosal rectal biopsies were used from 28 UC patients (15 without dysplasia and 13 with concurrent HGD or CA). The specimen slides were made using a touch prep method and underwent PWS analysis. We divided the patients into two groups: 13 as a training set and an independent 15 as a validation set. We identified six optical markers, ranked by measuring the information gain with respect to the outcome of cancer. The most effective markers were selected by maximizing the cross-validated training accuracy of a Naive Bayes classifier. The optimal classifier was applied to the validation data yielding 100% sensitivity and 75% specificity. Our results indicate that the PWS-derived optical markers can accurately predict UC patients with HGD/CA through assessment of rectal epithelial cells. By aiming for high sensitivity, our approach could potentially simplify the surveillance of UC patients and improve overall resource utilization by identifying patients with HGD/CA who should proceed with colonoscopy. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Recent Changes in UC Admissions Policies. Parent/Student Guide = Unos cambios recientes en los reglamentos de ingreso de la universidad de California. Guia de padres/estudiantes.

ERIC Educational Resources Information Center

EdSource, Inc., Palo Alto, CA.

This parent/student guide describes recent changes in admissions policies at the University of California (UC). Traditionally, UC admitted the top 12.5% of high school graduating seniors, but beginning in 2001, the top 4% of students in the graduating class of every high school are eligible if they have completed 11 specific "a-f"…

Family partnership and education interventions to reduce dietary sodium by patients with heart failure differ by family functioning.

PubMed

Dunbar, Sandra B; Clark, Patricia C; Stamp, Kelly D; Reilly, Carolyn M; Gary, Rebecca A; Higgins, Melinda; Kaslow, Nadine

2016-01-01

Determine if family functioning influences response to family-focused interventions aimed at reducing dietary sodium by heart failure (HF) patients. Lowering dietary sodium by HF patients often occurs within the home and family context. Secondary analysis of 117 dyads randomized to patient and family education (PFE), family partnership intervention (FPI) or usual care (UC). Dietary sodium measures were obtained from 3-day food record and 24-h urine samples. In the poor family functioning groups, FPI and PFE had lower mean urine sodium than UC (p < .05) at 4 months, and FPI remained lower than UC at 8 months (p < .05). For good family functioning groups, FPI and PFE had lower mean sodium levels by 3-day food record at 4 and 8 months compared to the UC group. Optimizing family-focused interventions into HF clinical care maybe indicated. Copyright © 2016 Elsevier Inc. All rights reserved.

Risk of colorectal cancer in patients with ulcerative colitis: a meta-analysis of population-based cohort studies.

PubMed

Jess, Tine; Rungoe, Christine; Peyrin-Biroulet, Laurent

2012-06-01

Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC). Studies examining the magnitude of this association have yielded conflicting results. We performed a meta-analysis of population-based cohort studies to determine the risk of CRC in patients with UC. We used MEDLINE, EMBASE, Cochrane, and CINAHL to perform a systematic literature search. We included 8 studies in the meta-analysis on the basis of strict inclusion and exclusion criteria. We calculated pooled standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for risk of CRC in patients with UC and performed meta-regression analyses of the effect of cohort size, calendar period, observation time, percentage with proctitis, and rates of colectomy on the risk of CRC. An average of 1.6% of patients with UC was diagnosed with CRC during 14 years of follow-up. SIRs ranged from 1.05 to 3.1, with a pooled SIR of 2.4 (95% CI, 2.1-2.7). Men with UC had a greater risk of CRC (SIR, 2.6; 95% CI, 2.2-3.0) than women (SIR, 1.9; 95% CI, 1.5-2.3). Young age was a risk factor for CRC (SIR, 8.6; 95% CI, 3.8-19.5; although this might have resulted from small numbers), as was extensive colitis (SIR, 4.8; 95% CI, 3.9-5.9). In meta-regression analyses, only cohort size was associated with risk of CRC. In population-based cohorts, UC increases the risk of CRC 2.4-fold. Male sex, young age at diagnosis with UC, and extensive colitis increase the risk. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Long-term follow-up reveals high incidence of colorectal cancer in Indian patients with inflammatory bowel disease.

PubMed

Bopanna, Sawan; Kedia, Saurabh; Das, Prasenjit; Dattagupta, S; Sreenivas, V; Mouli, V Pratap; Dhingra, Rajan; Pradhan, Rajesh; Kumar, N Suraj; Yadav, Dawesh P; Makharia, Govind; Ahuja, Vineet

2017-08-01

As the magnitude of sporadic colorectal cancer (CRC) in India is low, magnitude of CRC in ulcerative colitis (UC) is also considered low. As a result, screening for CRC in UC although advocated may not be followed everywhere. We report our data of UC-related CRC from a low-incidence area of sporadic CRC. A total of 1012 patients with left-sided colitis/pancolitis having more than one full-length colonoscopy performed at least a year after the onset of symptoms were included in retrospective analysis of prospectively maintained case records. In addition, 136 patients with duration of disease >10 years underwent surveillance white-light colonoscopy prospectively during the study period. A total of 1012 individuals were finally included (6542 person-years of follow-up, 68.5% males, disease duration: 6.4 ± 6.8 years). Twenty (1.97%) patients developed CRC. Two (10%) patients developed CRC during the first decade, 10/20 (50%) during the second and 8/20 (40%) after the second decade of disease. The cumulative risk of developing CRC was 1.5%, 7.2% and 23.6% in the first, second and third decade, respectively. Of 136 high-risk UC cases, five (3.6%) had CRC on screening colonoscopy. Disease duration and increasing age of onset were associated with higher risk of CRC. Cumulative risk of CRC in Indian UC patients is as high as 23.6% at 30 years. The risk of CRC increases with increasing age of onset and increasing duration of disease. A low risk of sporadic CRC does not confer a low risk of UC-related CRC, and regular screening is warranted.

High treatment persistence rate and significant endoscopic healing among real-life patients treated with vedolizumab - a Finnish Nationwide Inflammatory Bowel Disease Cohort Study (FINVEDO).

PubMed

Ylisaukko-Oja, Tero; Aaltonen, Jaakko; Nuutinen, Heikki; Blomster, Timo; Jussila, Airi; Pajala, Markku; Salminen, Kimmo; Moilanen, Veikko; Hakala, Kalle; Kellokumpu, Mikko; Toljamo, Kari; Rautiainen, Henna; Kuisma, Juha; Peräaho, Markku; Molander, Pauliina; Silvennoinen, Jouni; Liukkonen, Ville; Henricson, Hans; Tillonen, Jyrki; Esterinen, Mirva; Nielsen, Christian; Hirsi, Eija; Lääne, Margus; Suhonen, Ulla-Maija; Vihriälä, Ilkka; Mäkelä, Petri; Puhto, Mika; Punkkinen, Jari; Sulonen, Hannu; Herrala, Sauli; Jokelainen, Jari; Tamminen, Klaus; Sipponen, Taina

2018-02-01

The efficacy and tolerability of vedolizumab in the treatment of inflammatory bowel diseases (IBD) has been demonstrated in an extensive GEMINI clinical trial programme. Clinical trials represent highly selected patient populations and, therefore, it is important to demonstrate effectiveness in real-life clinical practice. We set out to assess real-world treatment outcomes of vedolizumab in a nationwide cohort of treatment refractory Finnish Crohn's disease (CD) and ulcerative colitis (UC) patients. This was a nationwide, retrospective, non-interventional, multi-centre chart review study. All adult patients from 27 Finnish gastroenterology centers with a diagnosis of UC or CD who had at least one vedolizumab infusion since the availability of the product in Finland, were included in the study. Data were collected retrospectively from medical charts at baseline, week 14, and month 6. The primary outcome measure was treatment persistence 24 weeks post-vedolizumab initiation. A total of 247 patients were included (108 CD, 139 UC). A total of 75.0% (n = 81) of all CD patients and 66.2% (n = 92) of all UC patients, were persistent on vedolizumab therapy for 6 months post treatment initiation. At month 6, 41.8% (28/67) of the treatment persistent CD patients and 73.3% (63/86) of the treatment persistent UC patients achieved clinical remission. Significant improvement in endoscopic scores were observed among treatment persistent patients (CD, n = 17, ΔSES-CD=-5.5, p = .008; UC, n = 26, ΔMayo endoscopic score =-0.5, p = .003) at month 6. Vedolizumab provides an effective and well-tolerated treatment option in real-world clinical practice even among treatment refractory IBD patients.

Ulcerative colitis associated with Takayasu's disease in two patients who received proctocolectomy.

PubMed

Masuda, Hideki; Ishii, Ukimoto; Aoki, Nobuhiko; Nakayama, Hisashi; Sato, Fumii; Karube, Hideaki; Suzuki, Shigeru; Kondo, Toshihiko

2002-01-01

Ulcerative colitis (UC) associated with Takayasu's disease (TD) is not common in Japan. Here, we report two patients with both diseases who received a total proctocolectomy. Patient 1, a 41-year-old woman with chronic continuous type UC, was first diagnosed with TD at the age of 10 years. Subsequently, she was diagnosed with UC and rectal cancer. HLA typing showed A2, A31(19), B52(5), and DR2(DRB1*1502). Coronary angiography showed 90% narrowing of the right coronary artery (RCA). After alleviating the RCA narrowing by percutaneous transluminal coronary angioplasty (PTCA), we performed a total proctocolectomy and ileostomy. Patient 2, a 20-year-old woman, was first diagnosed with TD at the age of 13 years. Severe symptoms, indicating fulminant UC, started 1 month prior to hospitalization. She was judged as needing surgery because the symptoms were not alleviated even with high doses of prednisolone. HLA typing showed A2, A31(19), B52, B61(40), DR2(DRB1*1502), and DR4 (DRB1*0405). Aortography showed a narrowing of the right renal artery; however, her renal function was normal. Based on these findings, we performed a three-stage operation for total proctocolectomy. Previously, we have reported that the DRB1*1502 and DRw11 genes were closely related to the intractability of UC. To date, we have not determined whether or how the DRB1*1502 gene might be related to TD. As the number of cases of UC associated with TD increases, it will be necessary to examine their DR2 subtypes.

Systematic Review with Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis.

PubMed