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Institution

Novartis

CompanyBasel, Switzerland
About: Novartis is a company organization based out in Basel, Switzerland. It is known for research contribution in the topics: Alkyl & Population. The organization has 41930 authors who have published 50566 publications receiving 1978996 citations. The organization is also known as: Novartis International AG.


Papers
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Journal ArticleDOI
TL;DR: The impact of irritable bowel syndrome, a gastrointestinal motility disorder, is underestimated and poorly quantified, as clinicians may see only a minority of sufferers.
Abstract: Summary Background : The impact of irritable bowel syndrome, a gastrointestinal motility disorder, is underestimated and poorly quantified, as clinicians may see only a minority of sufferers. Aim : To determine the prevalence, symptom patterns and impact of irritable bowel syndrome in the US. Methods : This two-phase community survey used quota sampling and random-digit telephone dialling (screening interview) to identify individuals with medically diagnosed irritable bowel syndrome or individuals not formally diagnosed, but fulfilling irritable bowel syndrome diagnostic criteria (Manning, Rome I or II). Information on irritable bowel syndrome symptoms, general health status, lifestyle and impact of symptoms on individuals’ lives was collected using in-depth follow-up interviews. Data were also collected for healthy controls identified in the screening interviews. Results : The total prevalence of irritable bowel syndrome in 5009 screening interviews was 14.1% (medically diagnosed: 3.3%; undiagnosed, but meeting irritable bowel syndrome criteria: 10.8%). Abdominal pain/discomfort was the most common symptom prompting consultation. Most sufferers (74% medically diagnosed; 63% undiagnosed) reported alternating constipation and diarrhoea. Previously diagnosed gastrointestinal disorders occurred more often in sufferers than non-sufferers. Irritable bowel syndrome sufferers had more days off work (6.4 vs. 3.0) and days in bed, and reduced activities to a greater extent than non-sufferers. Conclusions : Most (76.6%) irritable bowel syndrome sufferers in the US are undiagnosed. Irritable bowel syndrome has a substantial impact on sufferers’ well-being and health, with considerable socioeconomic consequences.

478 citations

Journal ArticleDOI
TL;DR: It is shown that complement, specifically, the membrane attack complex (MAC)-mediated arm of complement, is crucial to the development of arthritis in three different mouse models of osteoarthritis, and dysregulation of complement in synovial joints has a key role in the pathogenesis of arthritis.
Abstract: Osteoarthritis, characterized by the breakdown of articular cartilage in synovial joints, has long been viewed as the result of 'wear and tear'. Although low-grade inflammation is detected in osteoarthritis, its role is unclear. Here we identify a central role for the inflammatory complement system in the pathogenesis of osteoarthritis. Through proteomic and transcriptomic analyses of synovial fluids and membranes from individuals with osteoarthritis, we find that expression and activation of complement is abnormally high in human osteoarthritic joints. Using mice genetically deficient in complement component 5 (C5), C6 or the complement regulatory protein CD59a, we show that complement, specifically, the membrane attack complex (MAC)-mediated arm of complement, is crucial to the development of arthritis in three different mouse models of osteoarthritis. Pharmacological modulation of complement in wild-type mice confirmed the results obtained with genetically deficient mice. Expression of inflammatory and degradative molecules was lower in chondrocytes from destabilized joints from C5-deficient mice than C5-sufficient mice, and MAC induced production of these molecules in cultured chondrocytes. Further, MAC colocalized with matrix metalloprotease 13 (MMP13) and with activated extracellular signal-regulated kinase (ERK) around chondrocytes in human osteoarthritic cartilage. Our findings indicate that dysregulation of complement in synovial joints has a key role in the pathogenesis of osteoarthritis.

478 citations

Journal ArticleDOI
TL;DR: There is a paucity of biomarkers that reliably detect nephrotoxicity and the Predictive Safety Testing Consortium (PSTC) faced several challenges in identifying novel safety biomarkers in the renal setting.
Abstract: There is a paucity of biomarkers that reliably detect nephrotoxicity. The Predictive Safety Testing Consortium (PSTC) faced several challenges in identifying novel safety biomarkers in the renal setting.

478 citations

Journal ArticleDOI
TL;DR: To investigate the efficacy and safety of tegaserod, a novel 5‐HT4 receptor partial agonist, in a randomized, double‐blind, placebo‐controlled, 12‐week treatment, multicentre study.
Abstract: Aim: To investigate the efficacy and safety of tegaserod, a novel 5-HT4 receptor partial agonist, in a randomized, double-blind, placebo-controlled, 12-week treatment, multicentre study. Methods: Eight hundred and eighty-one patients with irritable bowel syndrome, characterized by abdominal pain, bloating and constipation, received tegaserod, 2 mg b.d. or 6 mg b.d., or placebo for 12 weeks. Results: Tegaserod, 2 mg b.d. and 6 mg b.d., showed a statistically significant relief of overall irritable bowel syndrome symptoms, measured by a weekly, self-administered questionnaire. At end-point, treatment differences from placebo were 12.7% and 11.8% for 2 mg b.d. and 6 mg b.d., respectively. The effect of tegaserod was noted as early as week 1, and was sustained over the 12-week treatment period. Individual irritable bowel syndrome symptoms assessed daily also showed a statistically significant improvement of abdominal discomfort/pain, number of bowel movements and stool consistency, and a favourable trend for reducing days with significant bloating. Adverse events were similar in all groups, with transient diarrhoea being the only adverse event seen more frequently with tegaserod than placebo. Conclusions: Based upon the results of this study, tegaserod offers rapid and sustained relief of the abdominal pain and constipation associated with irritable bowel syndrome. Tegaserod is also well tolerated.

477 citations

Journal ArticleDOI
TL;DR: This work provides the first evidence for the potential use of miRNAs as biomarkers of human drug‐induced liver injury by examining these molecules, for the first time, in humans with APAP poisoning.

477 citations


Authors

Showing all 41972 results

NameH-indexPapersCitations
Irving L. Weissman2011141172504
Peter J. Barnes1941530166618
Paul G. Richardson1831533155912
Kenneth C. Anderson1781138126072
Jie Zhang1784857221720
Lei Jiang1702244135205
Marc A. Pfeffer166765133043
Jorge E. Cortes1632784124154
Ian A. Wilson15897198221
Peter G. Schultz15689389716
Bruce D. Walker15577986020
Timothy P. Hughes14583191357
Kurt Wüthrich143739103253
Leonard Guarente14335280169
Christopher D.M. Fletcher13867482484
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202318
202285
20211,321
20201,377
20191,376
20181,456