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Sunanda V Kane

Publications and source records attributed to Sunanda V Kane.

14 recordsLinked to original sources
PubMed2007

Refined genomic localization and ethnic differences observed for the IBD5 association with Crohn's disease.

Although the general association of the inflammatory bowel disease (IBD) 5 region on chromosome 5q31 to Crohn's disease (CD) has been replicated repeatedly, the identity of the precise causal variant within the region remains unknown. A recent report proposed polymorphisms in solute carrier family 22, member 4 (SLC22A4) organic cation transporter 1(OCTN1) and solute carrier family 22, member 5 (SLC22A5) (OCTN2) as responsible for the IBD5 association, but definitive, large-sample comparison of those polymorphisms with others known to be in strong linkage disequilibrium was not performed. We evaluated 1879 affected offspring and parents ascertained by a North American IBD Genetics Consortium for six IBD5 tag single nucleotide polymorphisms (SNPs) to evaluate association localization and ethnic and subphenotypic specificity. We confirm association to the IBD5 region (best SNP IGR2096a_1/rs12521868, P<0.0005) and show this association to be exclusive to the non-Jewish (NJ) population (P=0.00005) (risk allele undertransmitted in Ashkenazi Jews). Using Phase II HapMap data, we demonstrate that there are a set of polymorphisms, spanning genes from prolyl 4-hydroxylase (P4HA2) through interferon regulatory factor 1 (IRF1) with equivalent statistical evidence of association to the reported SLC22A4 variant and that each, by itself, could entirely explain the IBD5 association to CD. Additionally, the previously reported SLC22A5 SNP is rejected as the potential causal variant. No specificity of association was seen with respect to disease type and location, and a modest association to ulcerative colitis is also observed. We confirm the importance of IBD5 to CD susceptibility, demonstrate that the locus may play a role in NJ individuals only, and establish that IRF1, PDLIM, and P4HA2 may be equally as likely to contain the IBD5 causal variant as the OCTN genes.

Adult↗
PubMed2006

The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial.

BACKGROUND: Alterations in gut flora may be important in the pathophysiology of the irritable bowel syndrome (IBS). OBJECTIVE: To determine whether the nonabsorbed antibiotic rifaximin is more effective than placebo in reducing symptoms in adults with IBS. DESIGN: Double-blind, randomized, placebo-controlled study. SETTING: 2 tertiary care medical centers. PARTICIPANTS: 87 patients who met Rome I criteria for IBS and were enrolled from December 2003 to March 2005. INTERVENTIONS: Participants who met enrollment criteria were randomly assigned to receive 400 mg of rifaximin 3 times daily for 10 days (n = 43) or placebo (n = 44). Eighty participants completed rifaximin therapy or placebo, and follow-up data were available for at least 34 participants per study group at any time point thereafter. MEASUREMENTS: A questionnaire was administered before treatment and 7 days after treatment. The primary outcome was global improvement in IBS. Patients were then asked to keep a weekly symptom diary for 10 weeks. RESULTS: Over the 10 weeks of follow-up, rifaximin resulted in greater improvement in IBS symptoms (P = 0.020). In addition, rifaximin recipients had a lower bloating score after treatment. LIMITATIONS: The major limitations of the study were its modest sample size and short duration and that most patients were from 1 center. CONCLUSIONS: Rifaximin improves IBS symptoms for up to 10 weeks after the discontinuation of therapy.

Adolescent↗
PubMed2006

Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease.

The intestinal epithelial barrier is frequently disrupted in inflammatory bowel disease (IBD) and this has been proposed to play a role in disease pathogenesis and reactivation. In vitro studies show that cytokine-induced epithelial barrier dysfunction can be mediated by increased myosin light chain kinase (MLCK) expression and subsequent myosin II regulatory light chain (MLC) phosphorylation. However, this has never been examined in human disease. The aim of these studies, therefore, was to determine whether MLCK is upregulated in the intestinal epithelium of IBD patients. MLCK expression and MLC phosphorylation in human intestinal resection and biopsy specimens were determined by quantitative immunofluorescence microscopy and correlated with clinical and histopathological data. The data show that ileal epithelial MLCK expression was mildly upregulated in inactive IBD. Expression increased further in active disease, with progressive increases in MLCK expression correlating positively with histological disease activity. This correlation between activity and MLCK expression was also seen in individual patients where areas of differing disease activity were analyzed. Colonic epithelial MLCK expression was similarly increased in active IBD and these increases also correlated positively with disease activity, both in individual patients and the overall study group. To evaluate MLCK enzymatic activity, MLC phosphorylation was assessed in snap-frozen colon biopsies. MLC phosphorylation was significantly increased in biopsies with active, but not inactive, IBD. Therefore, these data show that MLCK expression and enzymatic activity are increased in IBD. Moreover, the correlation with disease activity suggests that MLCK upregulation may contribute to barrier dysfunction and IBD pathogenesis.

Adult↗
PubMed2006

Factitious diarrhea masquerading as refractory celiac disease.

A 23-year-old female with a history of a histologically confirmed diagnosis of celiac disease was referred to our institution for refractory celiac disease for consideration of immunosuppressive therapy. Full workup revealed an elevated fecal magnesium level, and a concurrent diagnosis of laxative abuse was confirmed after discussion with the family. This case highlights the importance of considering factitious diarrhea in all patients admitted for refractory diarrhea, even those with documented underlying conditions.

Adult↗
PubMed2006

Inflammatory bowel disease characteristics among African Americans, Hispanics, and non-Hispanic Whites: characterization of a large North American cohort.

OBJECTIVES: Inflammatory bowel disease (IBD), comprising primarily of Crohn's disease (CD) and ulcerative colitis (UC), is increasingly prevalent in racial and ethnic minorities. This study was undertaken to characterize racial differences in disease phenotype in a predominantly adult population. METHODS: Phenotype data on 830 non-Hispanic white, 127 non-Hispanic African American, and 169 Hispanic IBD patients, recruited from six academic centers, were abstracted from medical records and compiled in the NIDDK-IBD Genetics Consortium repository. We characterized racial differences in family history, disease location and behavior, surgical history, and extraintestinal manifestations (EIMs) using standardized definitions. RESULTS: African American CD patients were more likely than whites to develop esophagogastroduodenal CD (OR = 2.8; 95% CI: 1.4-5.5), colorectal disease (OR = 1.9; 95% CI: 1.1-3.4), perianal disease (OR = 1.7; 95% CI: 1.03-2.8), but less likely to have ileal involvement (OR = 0.55; 95% CI: 0.32-0.96). They were also at higher risk for uveitis (OR = 5.5; 95% CI: 2.3-13.0) and sacroiliitis (OR = 4.0; 95% CI: 1.55-10.1). Hispanics had higher prevalence of perianal CD (OR = 2.9; 95% CI: 1.8-4.6) and erythema nodosum (3.3; 95% CI: 1.7-6.4). Among UC patients, Hispanics had more proximal disease extent. Both African American and Hispanic CD patients, but not UC patients, had lower prevalences of family history of IBD than their white counterparts. CONCLUSIONS: There are racial differences in IBD family history, disease location, and EIMs that may reflect underlying genetic variations and have important implications for diagnosis and management of disease. These findings underscore the need for further studies in minority populations.

Adult↗
PubMed2005

Tobacco use is associated with accelerated clinical recurrence of Crohn's disease after surgically induced remission.

GOALS: To study the association between tobacco exposure and postoperative clinical recurrence in Crohn's disease patients and quantify the time to clinical relapse following surgical resection. BACKGROUND: It is well accepted that cigarette smoking has a negative impact on postoperative course in Crohn's disease. However, the effect of smoking to hasten clinical recurrence has not been clearly delineated. STUDY: We reviewed medical records of patients undergoing surgical resection for medication-refractory disease within a 5-year period. Patients were followed for a period of 250 weeks. Outcomes were compared between smokers and nonsmokers and stratified by gender. RESULTS: Fifty-nine patients were studied. Sixty-nine percent of smokers versus 23% of nonsmokers had recurrent symptoms (P = 0.02) by the end of the observation period. There was no difference in the mean ages, gender, disease location, use of postoperative medications, or number of postoperative visits (P > 0.09). Smoking was associated with an increased risk of clinical recurrence [odds ratio 2.96 (95% confidence interval, CI 1.5-5.6)]. The time to clinical relapse for smokers was 130 weeks versus 234 weeks in nonsmokers (P < 0.001). CONCLUSION: Smoking is associated with clinical recurrence of Crohn's disease, and the time to clinical recurrence in smokers is shorter. Strategies for smoking cessation are warranted.

Adolescent↗
PubMed2004

Crohn's is not a 6-week disease: lifelong management of mild to moderate Crohn's disease.

Crohn's disease is an idiopathic, chronic inflammatory disorder of the digestive tract with heterogeneous clinical presentations. Crohn's is currently not a curable disease, and patients are faced with a lifetime of recurrent disease flare-ups and remissions. Management strategies for Crohn's must therefore be targeted toward lifelong management, taking into consideration not only the short-term but also the long-term aspects of the disease. With this in mind, here we review the classifications and natural history of Crohn's disease and discuss possible predictive factors for the disease evolution in a patient. Here we also evaluate the current preferable treatment practices, based on scientifically valid research and collective clinical experience, for the management of mild to moderate Crohn's disease.

Algorithms↗
PubMed2003

Defining complex contributions of NOD2/CARD15 gene mutations, age at onset, and tobacco use on Crohn's disease phenotypes.

BACKGROUND: Multiple factors, particularly IBD family history, tobacco use, age at diagnosis and recently, NOD2 mutant genotypes may influence Crohn's disease (CD) heterogeneity. METHODS: We performed a multicenter retrospective record analysis of 275 unrelated patients with CD. Age at diagnosis, IBD family history, Jewish ethnicity, tobacco use at diagnosis, surgical history, disease site and clinical behavior were correlated with genotypes for NOD2 mutations, and all risk factors were assessed for independent influence on outcomes of disease site, behavior and surgery free survival. RESULTS: Risk of ileal disease was increased for CD patients with two NOD2 mutations (Odds Ratio, O.R. 10.1), a smoking history (O.R. 2.25 per pack per day at diagnosis) or a younger age at diagnosis (O.R. 0.97 per each increased year). Presence of ileal disease (O.R. 4.8) and carrying one or two NOD2 mutations (O.R. 1.9 and 3.5, respectively) were independent risk factors for stricturing or non-perianal fistulizing behavior. Ileal disease, youthful onset and smoking at diagnosis (but not NOD2 mutations) were risk factors for early surgery. CONCLUSIONS: Carrying two NOD2 mutations predicts youthful onset, ileal disease involvement, and development of stricturing or non-perianal fistulizing complications. Smoking and early onset independently influence ileal site and time to surgery.

Adult↗
PubMed2003

Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation.

OBJECTIVE: Lactoferrin is a glycoprotein expressed by activated neutrophils. The aim of this study was to determine the sensitivity and specificity of fecal lactoferrin concentrations for inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) versus healthy controls. METHODS: Fresh stool samples were collected from outpatients with ulcerative colitis (UC), Crohn's disease (CD), or IBS. Clinical disease activity for IBD was assessed using a modified Harvey-Bradshaw Activity Index. Fecal lactoferrin concentrations were determined using a polyclonal antibody-based enzyme linked immunoassay. Mean fecal lactoferrin concentrations for each group and sensitivity and specificity of the assay were determined. RESULTS: One hundred-four CD patients, 80 UC patients, 31 IBS patients, and 56 healthy controls were recruited. The mean +/- SE fecal lactoferrin concentration (microg/g fecal weight) was 440 +/- 128 for CD patients, 1125 +/- 498 for UC patients, 1.27 +/- 0.29 for IBS patients, and 1.45 +/- 0.4 for healthy controls. Fecal lactoferrin was 90% specific for identifying inflammation in patients with active IBD. Elevated fecal lactoferrin was 100% specific in ruling out IBS. CONCLUSIONS: Fecal lactoferrin is sensitive and specific for detecting inflammation in chronic IBD. This noninvasive test may prove useful in screening for inflammation in patients presenting with abdominal pain and diarrhea.

Adolescent↗
PubMed2003

Novel therapies in the treatment of ulcerative colitis.

Ulcerative colitis is a chronic inflammatory disease of the colon of unknown cause. Its course is one of relapse and remission and requires therapy for both the induction and maintenance of remission. Progress in the fields of genetics and immunology affords important advances in our understanding of the inflammatory process. Traditional therapy for ulcerative colitis with nonspecific anti-inflammatories remains our gold standard. This review examines the most recent compounds in development for the treatment of ulcerative colitis, including data from early clinical trials and the potential clinical impact of future entities.

Adjuvants, Immunologic↗
PubMed2003

The efficacy of oral 5-ASAs in the treatment of active ulcerative colitis: a systematic review.

The authors set out to critically review the current data on the efficacy of oral 5-aminosalicylic acid (5-ASA) agents for active ulcerative colitis (UC). Thirty-one studies were identified; 19 met entry criteria. Three trials with mesalamine showed statistical significance versus placebo; those with olsalazine or balsalazide did not. No agent was statistically different from sulfasalazine. In 2 of 3 trials of balsalazide versus mesalamine, results for defined primary and secondary endpoints failed to demonstrate statistically significant differences. Studies suggest that mesalamine is superior to placebo for treating active UC. Five-ASA products appear to be as effective as sulfasalazine, but available data do not suggest a difference in efficacy between any of the 5-ASA preparations.

Administration, Oral↗