Publications by authors named "Raheel Khan"

15 Publications

  • Page 1 of 1

Abdominal Pain Caused by Occlusion of the Celiac Trunk and Superior Mesenteric Artery in Addition to Irritable Bowel Syndrome: Case Series and Literature Review.

Cureus 2021 Jun 17;13(6):e15729. Epub 2021 Jun 17.

Medicine, Qatar University, Doha, QAT.

Irritable bowel syndrome (IBS) is a benign condition of the gastrointestinal tract causing abdominal pain, bloating, diarrhea, and/or constipation. Symptoms of IBS usually improve on passing flatus and defecation. There is no known identifiable underlying pathology; however, several risk factors are known to contribute to the development of IBS, which include a stressful lifestyle and certain foods such as bread, coffee, alcohol, pasta, and chocolates. Intestinal bacteria may also contribute to symptoms of IBS. IBS is diagnosed clinically and treated with various medications to control the symptoms. On the other hand, celiac and mesenteric artery thrombosis (CAMAT) is a condition that may cause significantly higher mortality and morbidity if not recognized early. CAMAT leads to the blockage of major blood vessels to the intestine and several abdominal viscera leading to abdominal pain, nausea, sweating, and, in some cases, symptoms of shock. CAMAT is most likely caused by thrombosis; however, occasionally, embolisms from distant sources in patients with atrial fibrillation can also contribute to the development of CAMAT. CAMAT is usually diagnosed with a computed tomography angiogram (CTA) and treated either surgically or medically with anticoagulants. Vascular thrombus in the thoracic and abdominal region causing ischemia of the stomach and abdominal pain in patients with a history of IBS can easily be missed and cause grave complications with high morbidity and mortality. We present two cases who were initially diagnosed and treated for IBS and later diagnosed with serious intra-abdominal pathology of CAMAT thrombosis. The first case is of a 55-year-old female who was previously diagnosed with IBS and was treated with mebeverine 200mg twice daily and esomeprazole 20mg once daily for 10 weeks. Her pain continued to get worse and she presented to the emergency department by ambulance. She underwent CTA, which showed occlusion of the celiac trunk and superior mesenteric artery causing liver and splenic infarcts. The patient received heparin and underwent a thrombectomy and embolectomy of the superior mesenteric and celiac arteries. No significant abnormality was found in the blood results. Thrombophilia screening was negative. The patient was discharged on warfarin. The second case is of a 53-year-old man who was also initially diagnosed with IBS and was treated with mebeverine 200mg twice daily for eight weeks before presenting to the emergency department with worsening abdominal pain. He underwent a CTA with contrast, which showed occlusion of the common hepatic artery and stenosis of the splenic artery leading to multiple splenic infarcts. No significant abnormality was found in blood test. Thrombophilia screening was negative. He was treated with new anticoagulant medication, dabigatran 150 mg orally twice daily. Both patients were managed with successful outcomes and were discharged home on anticoagulants. There was no recurrence of symptoms at three-month follow-up. These cases highlight that a secondary cause of symptoms such as vascular thrombosis must be sought for patients who fail to improve with conservative management of IBS.
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http://dx.doi.org/10.7759/cureus.15729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286357PMC
June 2021

Functional repertoire of protein kinases and phosphatases in synaptic plasticity and associated neurological disorders.

Neural Regen Res 2021 Jun;16(6):1150-1157

Centre for Advanced Computational Solutions (C-fACS), Lincoln University, Christchurch, New Zealand.

Protein phosphorylation and dephosphorylation are two essential and vital cellular mechanisms that regulate many receptors and enzymes through kinases and phosphatases. Ca- dependent kinases and phosphatases are responsible for controlling neuronal processing; balance is achieved through opposition. During molecular mechanisms of learning and memory, kinases generally modulate positively while phosphatases modulate negatively. This review outlines some of the critical physiological and structural aspects of kinases and phosphatases involved in maintaining postsynaptic structural plasticity. It also explores the link between neuronal disorders and the deregulation of phosphatases and kinases.
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http://dx.doi.org/10.4103/1673-5374.300331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224123PMC
June 2021

Cigarette Smoke and Nicotine-Containing Electronic-Cigarette Vapor Downregulate Lung WWOX Expression, Which Is Associated with Increased Severity of Murine Acute Respiratory Distress Syndrome.

Am J Respir Cell Mol Biol 2021 01;64(1):89-99

Division of Pulmonary, Critical Care, Sleep and Allergy Medicine, University of Illinois, Chicago, Illinois.

A history of chronic cigarette smoking is known to increase risk for acute respiratory distress syndrome (ARDS), but the corresponding risks associated with chronic e-cigarette use are largely unknown. The chromosomal fragile site gene, WWOX, is highly susceptible to genotoxic stress from environmental exposures and thus an interesting candidate gene for the study of exposure-related lung disease. Lungs harvested from current versus former/never-smokers exhibited a 47% decrease in WWOX mRNA levels. Exposure to nicotine-containing e-cigarette vapor resulted in an average 57% decrease in WWOX mRNA levels relative to vehicle-treated controls. In separate studies, endothelial (EC)-specific WWOX knockout (KO) versus WWOX flox control mice were examined under ARDS-producing conditions. EC WWOX KO mice exhibited significantly greater levels of vascular leak and histologic lung injury. ECs were isolated from digested lungs of untreated EC WWOX KO mice using sorting by flow cytometry for CD31 CD45cells. These were grown in culture, confirmed to be WWOX deficient by RT-PCR and Western blotting, and analyzed by electric cell impedance sensing as well as an FITC dextran transwell assay for their barrier properties during methicillin-resistant or LPS exposure. WWOX KO ECs demonstrated significantly greater declines in barrier function relative to cells from WWOX flox controls during either methicillin-resistant or LPS treatment as measured by both electric cell impedance sensing and the transwell assay. The increased risk for ARDS observed in chronic smokers may be mechanistically linked, at least in part, to lung WWOX downregulation, and this phenomenon may also manifest in the near future in chronic users of e-cigarettes.
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http://dx.doi.org/10.1165/rcmb.2020-0145OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780991PMC
January 2021

Feasibility of Repurposing Clioquinol for Cancer Therapy.

Recent Pat Anticancer Drug Discov 2020 ;15(1):14-31

Departments of Oncology, Pharmacology, and Pathology, School of Medicine, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, United States.

Background: Cancer is a prevalent disease in the world and is becoming more widespread as time goes on. Advanced and more effective chemotherapeutics need to be developed for the treatment of cancer to keep up with this prevalence. Repurposing drugs is an alternative to discover new chemotherapeutics. Clioquinol is currently being studied for reposition as an anti-cancer drug.

Objective: This study aimed to summarize the anti-cancer effects of clioquinol and its derivatives through a detailed literature and patent review and to review their potential re-uses in cancer treatment.

Methods: Research articles were collected through a PubMed database search using the keywords "Clioquinol" and "Cancer." The keywords "Clioquinol Derivatives" and "Clioquinol Analogues" were also used on a PubMed database search to gather research articles on clioquinol derivatives. Patents were gathered through a Google Patents database search using the keywords "Clioquinol" and "Cancer."

Results: Clioquinol acts as a copper and zinc ionophore, a proteasome inhibitor, an anti-angiogenesis agent, and is an inhibitor of key signal transduction pathways responsible for its growth-inhibitory activity and cytotoxicity in cancer cells preclinically. A clinical trial conducted by Schimmer et al., resulted in poor outcomes that prompted studies on alternative clioquinol-based applications, such as new combinations, new delivery methods, or new clioquinol-derived analogues. In addition, numerous patents claim alternative uses of clioquinol for cancer therapy.

Conclusion: Clioquinol exhibits anti-cancer activities in many cancer types, preclinically. Low therapeutic efficacy in a clinical trial has prompted new studies that aim to discover more effective clioquinol- based cancer therapies.
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http://dx.doi.org/10.2174/1574892815666200227090259DOI Listing
January 2021

Repurposing Disulfiram as An Anti-Cancer Agent: Updated Review on Literature and Patents.

Recent Pat Anticancer Drug Discov 2019 ;14(2):113-132

Departments of Oncology, Pharmacology & Pathology, School of Medicine, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, United States.

Background: Despite years of success of most anti-cancer drugs, one of the major clinical problems is inherent and acquired resistance to these drugs. Overcoming the drug resistance or developing new drugs would offer promising strategies in cancer treatment. Disulfiram, a drug currently used in the treatment of chronic alcoholism, has been found to have anti-cancer activity.

Objective: To summarize the anti-cancer effects of Disulfiram through a thorough patent review.

Methods: This article reviews molecular mechanisms and recent patents of Disulfiram in cancer therapy.

Results: Several anti-cancer mechanisms of Disulfiram have been proposed, including triggering oxidative stress by the generation of reactive oxygen species, inhibition of the superoxide dismutase activity, suppression of the ubiquitin-proteasome system, and activation of the mitogen-activated protein kinase pathway. In addition, Disulfiram can reverse the resistance to chemotherapeutic drugs by inhibiting the P-glycoprotein multidrug efflux pump and suppressing the activation of NF-kB, both of which play an important role in the development of drug resistance. Furthermore, Disulfiram has been found to reduce angiogenesis because of its metal chelating properties as well as its ability to inactivate Cu/Zn superoxide dismutase and matrix metalloproteinases. Disulfiram has also been shown to inhibit the proteasomes, DNA topoisomerases, DNA methyltransferase, glutathione S-transferase P1, and O6- methylguanine DNA methyltransferase, a DNA repair protein highly expressed in brain tumors. The patents described in this review demonstrate that Disulfiram is useful as an anti-cancer drug.

Conclusion: For years the FDA-approved, well-tolerated, inexpensive, orally-administered drug Disulfiram was used in the treatment of chronic alcoholism, but it has recently demonstrated anti-cancer effects in a range of solid and hematological malignancies. Its combination with copper at clinically relevant concentrations might overcome the resistance of many anti-cancer drugs in vitro, in vivo, and in patients.
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http://dx.doi.org/10.2174/1574892814666190514104035DOI Listing
February 2020

Acute Hepatitis in Infections Caused by Dengue Virus in Southern Punjab, Pakistan.

Cureus 2018 Dec 28;10(12):e3788. Epub 2018 Dec 28.

Internal Medicine, Quaid-E-Azam Medical College, Bahawalpur, PAK.

Background Dengue is the most common vector-borne disease worldwide. It poses a significant health burden in tropical and subtropical countries. Common clinical presentations include retro-orbital pain, fever, headache, nausea, vomiting and aches and pains in the body. A severe form of dengue fever is known as dengue hemorrhagic fever (DHF) that includes signs of hemorrhage. Besides the typical signs and symptoms, atypical presentations of dengue include myositis, hepatitis and encephalitis. Hepatic involvement in dengue has varied presentations. This study aims to highlight the importance of acute hepatitis, an atypical presentation in dengue patients. Methods  We conducted a descriptive, cross-sectional study in the Medical Unit-1 of Bahawal Victoria Hospital, Bahawalpur, a tertiary-care hospital serving the area of Southern Punjab, Pakistan. The relevant medical records of 63 patients admitted with dengue-associated hepatitis to the Medical Unit-1 of Bahawal Victoria Hospital, Bahawalpur, between January 1, 2015 and December 1, 2016, were reviewed. Informed consent was given. Information regarding demographic variables and disease course was collected and analyzed. Results  This study included 55 men (87.3%) and eight (12.7%) women. Fifty (79.3%) patients were diagnosed with dengue fever (DF). Thirteen patients were managed on the lines of DHF. Out of the total 63 patients, only six were locals. The common clinical presentations in these patients included high fever, retro-orbital pain, severe headache, rash, dark-colored urine, bleeding problems and hepatomegaly. Higher levels of aspartate aminotransferase (AST) were noted in comparison to alanine transferase (ALT). Despite the complicated clinical course in some patients, all patients were managed successfully and discharged, except one. Conclusion The frequency of acute hepatitis in dengue patients is high, especially in young men. Early diagnosis and prompt treatment are necessary for better prognosis. Although no specific treatment guidelines are available, supportive treatment in a timely fashion can prevent complications. Transfusion with packed cell volume (PCV) and N-acetyl cysteine (NAC) has produced promising results.
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http://dx.doi.org/10.7759/cureus.3788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402748PMC
December 2018

Progress Of Khyber Pakhtunkhwa (Pakistan) Towards Universal Health Coverage.

J Ayub Med Coll Abbottabad 2018 Jul-Sep;30(3):482-485

State life Insurance Corporation of Pakistan.

Background: Khyber Pakhtunkhwa (KP) launched its flagship Social health protection initiative (SHPI), named Sehat Sahulat Program (SSP). SSP envisions to improve access to healthcare for poorest of the poor and contribute towards achieving Universal Health Coverage (UHC). Current study was undertaken to analyze SSP in context of UHC framework i.e. to see as to (i) who is covered, (ii) what services are covered, and (iii) what extent of financial protection is conferred.

Methods: We conducted thorough archival research. Official documents studied were concept paper(s), approved planning commission documents (PC-1 forms) and signed agreement(s) between government of KP and the insurance firm.

Results: SSP enrolled poorest 51% of province' population i.e. 14.4 million people. It covers for all secondary and limited tertiary services. Maximum expenditure limit per family per year is Rs.540, 000/-. Government pays a premium of Rs.1549/- per year per household to 3rd party (insurance firm) which ensures services through a mix of public-private providers.

Conclusions: The breadth, depth and height of SSP are significant. It is a phenomenal progress towards achieving UHC.
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January 2019

Political Architecture And Legal Framework Related To Social Health Protection Schemes In Pakistan: Qualitative Inquiry Of Policy Makers' Viewpoint.

J Ayub Med Coll Abbottabad 2018 Jul-Sep;30(3):389-396

Peshawar Medical College, Peshawar, Pakistan.

Background: Pakistan is a federal state with three tiers of government. Following contentious general elections in 2013, ever first democratic transition took place in Pakistan. Subsequently, two social health protection schemes were launched. Current paper's objective is to understand the political context in which these schemes were launched and to explore the constitutional position of access to healthcare in Pakistan. This paper also explores the legal protection/ sustainability with regards to these schemes.

Methods: We used qualitative research techniques with interpretivist paradigm and case-study approach. In-depth interviews were conducted, followed by content analysis. Triangulation and data saturation were observed to guide our sample size. Officials involved with these schemes at policy and implementation level were interviewed. Ethical approval was taken from ethics board of Khyber Medical University. Based on purposive sampling, in-depth interviews were conducted and thematic analysis was performed.

Results: We identified two themes in response to question-1 of our interview, asking about the cause of action behind starting these schemes and their legal protection. These themes were: (i) [initiation of] Social Health Protection as democratization of healthcare, and (ii) [initiation of] Social health protection in legal void. Implicitly, these schemes are a product of grass root political activism and health found berth in election manifestos recently. Also, we deduce that health is not a constitutional right in Pakistan. These schemes lack constitutional guarantee and ensued in absence of overarching legal framework.

Conclusions: These social health protection schemes are high on political agenda but lack constitutional and legal protection.
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January 2019

Political Architecture And Legal Framework Related To Social Health Protection Schemes In Pakistan: Qualitative Inquiry Of Policy Makers' Viewpoint.

J Ayub Med Coll Abbottabad 2018 Jul-Sep;30(3):389-396

Peshawar Medical College, Peshawar, Pakistan.

Background: Pakistan is a federal state with three tiers of government. Following contentious general elections in 2013, ever first democratic transition took place in Pakistan. Subsequently, two social health protection schemes were launched. Current paper's objective is to understand the political context in which these schemes were launched and to explore the constitutional position of access to healthcare in Pakistan. This paper also explores the legal protection/ sustainability with regards to these schemes.

Methods: We used qualitative research techniques with interpretivist paradigm and case-study approach. In-depth interviews were conducted, followed by content analysis. Triangulation and data saturation were observed to guide our sample size. Officials involved with these schemes at policy and implementation level were interviewed. Ethical approval was taken from ethics board of Khyber Medical University. Based on purposive sampling, in-depth interviews were conducted and thematic analysis was performed.

Results: We identified two themes in response to question-1 of our interview, asking about the cause of action behind starting these schemes and their legal protection. These themes were: (i) [initiation of] Social Health Protection as democratization of healthcare, and (ii) [initiation of] Social health protection in legal void. Implicitly, these schemes are a product of grass root political activism and health found berth in election manifestos recently. Also, we deduce that health is not a constitutional right in Pakistan. These schemes lack constitutional guarantee and ensued in absence of overarching legal framework.

Conclusions: These social health protection schemes are high on political agenda but lack constitutional and legal protection.
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January 2019

Omental Infarction: An Unusual Cause of Left-Sided Abdominal Pain.

ACG Case Rep J 2014 Jul 8;1(4):223-4. Epub 2014 Jul 8.

Department of Pediatrics, West Virginia University, Charleston, WV.

Left-sided omental infarction (OI) is rare in both the adult and pediatric patients. To our knowledge, only 2 pediatric cases of a left-sided OI have been reported in the literature. We report a case of an obese 13-year-old male who presented with a 6-day history of intermittent, colicky, left upper quadrant abdominal pain.
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http://dx.doi.org/10.14309/crj.2014.60DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4435328PMC
July 2014

Pulmonary nocardiosis in an adolescent patient with Crohn's disease treated with infliximab: a serious complication of TNF-alpha blockers.

W V Med J 2015 May-Jun;111(3):36-9

Nocardiosis is a serious complication of tumor necrosis factor (TNF) alpha blockers. With the increasing use of biologics for inflammatory bowel disease, it is to be anticipated that opportunistic infections such as nocardia will be more frequently encountered in children. We present the case of a 16 year old male with Crohn's disease who developed pulmonary nocardiosis during the course of his treatment with infliximab. This case illustrates the diagnostic and therapeutic challenges faced in patients with inflammatory bowel disease infected with opportunistic organisms. Pediatric health care providers need to be aware so that early diagnosis and treatment can be provided thereby preventing disseminated disease and having favorable outcomes. Although TNF blocker therapy must be discontinued in the presence of such infections, biologic therapy may be reintroduced after successful treatment with trimethoprim-sulfamethoxazole to control underlying symptoms of inflammatory bowel disease.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003015PMC
June 2015

Cytomegaloviral enteritis: a rare cause of small gut perforation.

J Ayub Med Coll Abbottabad 2011 Oct-Dec;23(4):133-4

Department of Surgery, Military Hospital, Rawalpindi, Pakistan.

A 47-year-old man was admitted with four months history of pain upper central abdomen associated with passage of 3-4 loose watery stools per day. Abdominal examination revealed soft abdomen with mild tenderness in the para-umbilical region. There was associated hepatomegaly. His Hb% was low, liver and renal functions were deranged. Upper GI endoscopy revealed antral ulcer, and colonoscopy revealed a caecal ulcer, which were biopsied. Liver biopsy was also done. Histopathology report showed evidence of inflammatory colitis and chronic hepatitis, so a diagnosis of inflammatory bowel disease with autoimmune hepatitis was made. He was negative for HIV and hepatitis serology. He was given long list of medicine including steroids but the symptoms did not improve. Two months after admission he developed severe abdominal pain associated with distension. The X-Ray chest revealed pneumoperitoneum and laparotomy was carried out which revealed a small perforation in terminal ileum associated with multiple circular indurated areas ranging from few mm to 1.5 Cm in size with central thinning spread over distal half of small gut and enlarged mesenteric lymph nodes. The biopsy of perforated area revealed cytomegaloviral enteritis. Postoperatively patient developed ARDS and died on 13th postoperative day.
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April 2013

Safety and pharmacokinetics of ribavirin for the treatment of la crosse encephalitis.

Pediatr Infect Dis J 2011 Oct;30(10):860-5

Department of Pediatrics, West Virginia University Health Sciences Center, Charleston Division, Charleston, WV, USA.

Background: La Crosse viral encephalitis (LACVE) is associated with residual epilepsy and neurocognitive deficits in survivors. This report summarizes 3 phases of clinical studies of children treated with intravenous (IV) ribavirin (RBV), each one exploring a different phase (I, IIA, IIB) of clinical trial development.

Methods: In phase I, 7 children with life-threatening LACVE were treated with emergency use RBV using a moderate IV dose (8.33 mg/kg/dose q 8 hours day 1, 5 mg/kg/dose q 8 hours days 2-10). In phase IIA, 12 children with severe LACVE were enrolled: 8 treated with RBV (same dose as phase I) and 4 with placebo. In phase IIB an escalated dose was used (33 mg/kg dose 1, then 16 mg/kg/dose q 6 hours for 4 days, and 8 mg/kg/dose q 8 hours for 3 days).

Results: In a group of 15 children treated in phase I and phase IIA, RBV appeared safe at moderate dose, but based on steady-state RBV levels of 9.3 μM, estimated cerebrospinal fluid levels were less than 20% of the EC50 of RBV for LACVE. At the escalated dose used in phase IIB, adverse events occurred, likely related to RBV, and therefore the trial was discontinued. Nevertheless, valuable pharmacokinetic (PK) and safety data were obtained at moderate dose, with potential treatment implications for other indications.

Conclusions: Although the results do not support the use of RBV for LACVE, this nevertheless is the largest study of antiviral treatment for LACVE to date and the largest pharmacokinetic analysis of IV RBV in children for any indication.
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http://dx.doi.org/10.1097/INF.0b013e31821c922cDOI Listing
October 2011

Delirium: sifting through the confusion.

Curr Psychiatry Rep 2009 Jun;11(3):226-34

Department of Psychiatry and Behavioral Sciences, University of California, Davis Medical Center, 2230 Stockton Boulevard, Sacramento, CA 95817, USA.

Delirium is commonly encountered in the hospital setting, particularly in the intensive care unit. However, the diagnosis is often missed, due in part to the nature of the illness, fluctuating levels of consciousness, and varied presentation. Even when it is recognized, delirium can be hard to manage, with multiple factors contributing to its course. In this article, we review the latest information regarding the underlying mechanisms of the syndrome and treatment options available. This is accomplished by examining two complex cases encountered at a university medical center-based psychosomatic service.
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http://dx.doi.org/10.1007/s11920-009-0035-8DOI Listing
June 2009

Gastrointestinal norovirus infection associated with exacerbation of inflammatory bowel disease.

J Pediatr Gastroenterol Nutr 2009 Mar;48(3):328-33

Department of Pediatrics, West Virginia University Health Sciences Center, Charleston, WV, USA.

Objective: In this study we aimed to determine, in pediatric patients, whether norovirus infection could be associated with exacerbations of inflammatory bowel disease (IBD) and ascertain whether the clinical expression of norovirus gastroenteritis was similar in patients with IBD compared with non-IBD controls.

Materials And Methods: We performed a case-control retrospective chart review, over a 10-month interval, of patients with IBD with an exacerbation of their disease. The presence of norovirus in stool and/or rectal swab samples, as determined by an enzyme-linked immunoassay, was assessed. In addition, sex, age, type of IBD, presence or absence of diarrhea, hematochezia, and the need for hospitalization were determined. A similar number of control patients who did not have IBD were used as controls.

Results: Nine patients with IBD (8 ulcerative colitis/1 Crohn disease) had exacerbations with diarrhea. Eight had norovirus antigen in at least 1 sample. All 9 patients with IBD presented with bloody diarrhea and 6 of the 8 norovirus-positive patients with IBD required hospitalization. All of the control patients experienced diarrhea; however, no hematochezia was noted and no hospitalization was required. Several patients with IBD and controls remained positive for norovirus months after the initial positive stool and/or rectal swab sample. The virus appeared to be more common during winter months.

Conclusions: We conclude that norovirus may be associated with exacerbations of IBD. When norovirus accompanies IBD it is more likely to be associated with hematochezia than when the infection occurs in the absence of IBD.
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http://dx.doi.org/10.1097/mpg.0b013e31818255ccDOI Listing
March 2009
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