D C Whitcomb

Summary

Affiliation: University of Pittsburgh
Country: USA

Publications

  1. ncbi request reprint Gene-environment factors that contribute to alcoholic pancreatitis in humans
    David C Whitcomb
    Division of Gastroenterology, Department of Medicine, University of Pittsburgh, and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA
    J Gastroenterol Hepatol 21:S52-5. 2006
  2. pmc Genetic risk factors for pancreatic disorders
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Department of Cell Biology and Molecular Physiology, and Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania Electronic address
    Gastroenterology 144:1292-302. 2013
  3. pmc Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Nat Genet 44:1349-54. 2012
  4. doi request reprint Genetics of alcoholic and nonalcoholic pancreatitis
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Cell Biology and Physiology, and Human Genetics, University of Pittsburgh and UPMC, Pittsburgh, Pennsylvania 15213, USA
    Curr Opin Gastroenterol 28:501-6. 2012
  5. pmc What is personalized medicine and what should it replace?
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Medical Arts Building, 3708 Fifth Avenue, Suite 401 5, Pittsburgh, PA 15213, USA
    Nat Rev Gastroenterol Hepatol 9:418-24. 2012
  6. pmc Whole exome sequencing identifies multiple, complex etiologies in an idiopathic hereditary pancreatitis kindred
    Jessica Larusch
    Department of Medicine, University of Pittsburgh Pittsburgh, PA, USA
    JOP 13:258-62. 2012
  7. pmc Does the pain-protective GTP cyclohydrolase haplotype significantly alter the pattern or severity of pain in humans with chronic pancreatitis?
    Mark Lazarev
    Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Mol Pain 4:58. 2008
  8. pmc Going MAD: development of a "matrix academic division" to facilitate translating research to personalized medicine
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
    Acad Med 86:1353-9. 2011
  9. pmc Value of genetic testing in the management of pancreatitis
    D C Whitcomb
    GI Administration, Mezzanine Level, C Wing, UPMC Presbyterian, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Gut 53:1710-7. 2004
  10. ncbi request reprint Genetic predisposition to alcoholic chronic pancreatitis
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, and the VA Pittsburgh Health Care System, Pittsburgh, Pennsylvania, USA
    Pancreas 27:321-6. 2003

Research Grants

Detail Information

Publications111 found, 100 shown here

  1. ncbi request reprint Gene-environment factors that contribute to alcoholic pancreatitis in humans
    David C Whitcomb
    Division of Gastroenterology, Department of Medicine, University of Pittsburgh, and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA
    J Gastroenterol Hepatol 21:S52-5. 2006
    ..Human studies suggest that PRSS1 and SPINK1 mutation increase the pancreas' susceptibility to alcohol-associated pancreatitis, and that tobacco smoking, and some factors, affect disease progression...
  2. pmc Genetic risk factors for pancreatic disorders
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Department of Cell Biology and Molecular Physiology, and Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania Electronic address
    Gastroenterology 144:1292-302. 2013
    ..Learning how various genetic factors affect pancreatic cells and systems could lead to etiology-based therapies rather than treatment of symptoms...
  3. pmc Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Nat Genet 44:1349-54. 2012
    ..These results could partially explain the high frequency of alcohol-related pancreatitis in men (male hemizygote frequency is 0.26, whereas female homozygote frequency is 0.07)...
  4. doi request reprint Genetics of alcoholic and nonalcoholic pancreatitis
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Cell Biology and Physiology, and Human Genetics, University of Pittsburgh and UPMC, Pittsburgh, Pennsylvania 15213, USA
    Curr Opin Gastroenterol 28:501-6. 2012
    ..To provide an expert review and expert perspective on important advances related to the genetics of acute and chronic pancreatitis...
  5. pmc What is personalized medicine and what should it replace?
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Medical Arts Building, 3708 Fifth Avenue, Suite 401 5, Pittsburgh, PA 15213, USA
    Nat Rev Gastroenterol Hepatol 9:418-24. 2012
    ....
  6. pmc Whole exome sequencing identifies multiple, complex etiologies in an idiopathic hereditary pancreatitis kindred
    Jessica Larusch
    Department of Medicine, University of Pittsburgh Pittsburgh, PA, USA
    JOP 13:258-62. 2012
    ....
  7. pmc Does the pain-protective GTP cyclohydrolase haplotype significantly alter the pattern or severity of pain in humans with chronic pancreatitis?
    Mark Lazarev
    Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Mol Pain 4:58. 2008
    ....
  8. pmc Going MAD: development of a "matrix academic division" to facilitate translating research to personalized medicine
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
    Acad Med 86:1353-9. 2011
    ..The author illustrates this approach by describing its successful application to the reverse engineering of chronic pancreatitis...
  9. pmc Value of genetic testing in the management of pancreatitis
    D C Whitcomb
    GI Administration, Mezzanine Level, C Wing, UPMC Presbyterian, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Gut 53:1710-7. 2004
  10. ncbi request reprint Genetic predisposition to alcoholic chronic pancreatitis
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, and the VA Pittsburgh Health Care System, Pittsburgh, Pennsylvania, USA
    Pancreas 27:321-6. 2003
    ..New genetic, environmental, and triggering factors must be considered to gain further insight into the mechanisms leading to alcoholic chronic pancreatitis so that strategies for treatment and prevention can be developed...
  11. ncbi request reprint Hereditary pancreatitis: a model for understanding the genetic basis of acute and chronic pancreatitis
    D C Whitcomb
    Departments of Medicine, Cell Biology and Physiology, and Human Genetics, University of Pittsburgh, VA Pittsburgh Health Care System, Pittsburgh, PA, USA
    Pancreatology 1:565-70. 2001
    ..The availability of new genetic information and genomic tools should produce a revolution in our understanding of pancreatic diseases...
  12. ncbi request reprint Inflammation and Cancer V. Chronic pancreatitis and pancreatic cancer
    David C Whitcomb
    UPMC Presbyterian, GI Div, Mezzanine 2, C Wing, 200 Lothrop St, Pittsburgh, PA 15213, USA
    Am J Physiol Gastrointest Liver Physiol 287:G315-9. 2004
    ....
  13. ncbi request reprint A systems biology approach to genetic studies of pancreatitis and other complex diseases
    D C Whitcomb
    Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Cell Mol Life Sci 64:1763-77. 2007
    ....
  14. doi request reprint Genetics and alcohol: a lethal combination in pancreatic disease?
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh and UPMC, Pennsylvania 15213, USA
    Alcohol Clin Exp Res 35:838-42. 2011
    ..These studies and others also defined distinctive roles of alcohol and genetics in the etiology and progression of chronic pancreatitis...
  15. ncbi request reprint A mathematical model of the pancreatic duct cell generating high bicarbonate concentrations in pancreatic juice
    David C Whitcomb
    Department of Medicine, University of Pittsburgh, UPMC Presbyterian, Pittsburgh, Pennsylvania 15213, USA
    Pancreas 29:e30-40. 2004
    ..To develop a simple, physiologically based mathematical model of pancreatic duct cell secretion using experimentally derived parameters that generates pancreatic fluid bicarbonate concentrations of >140 mM after CFTR activation...
  16. doi request reprint Angiopoietin-2, a regulator of vascular permeability in inflammation, is associated with persistent organ failure in patients with acute pancreatitis from the United States and Germany
    David C Whitcomb
    Department of Medicine, University of Pittsburgh Medical Center, Pennsylvania, USA
    Am J Gastroenterol 105:2287-92. 2010
    ..The aim of this study was to determine whether Ang-1 and/or Ang-2 levels are predictive biomarkers of persistent organ failure (>48 h) and prolonged hospital course...
  17. doi request reprint Genetic aspects of pancreatitis
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Annu Rev Med 61:413-24. 2010
    ..Multiple studies are reporting new polymorphisms, as well as complex gene x gene and gene x environmental interactions...
  18. doi request reprint Germ-line mutations, pancreatic inflammation, and pancreatic cancer
    David Whitcomb
    Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Clin Gastroenterol Hepatol 7:S29-34. 2009
    ..Because we cannot change our genes, lifestyle choices are currently the best way to reduce pancreatic cancer risk until more effective preventative strategies are developed...
  19. doi request reprint Pancrelipase delayed-release capsules (CREON) for exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery: A double-blind randomized trial
    David C Whitcomb
    Department of Medicine, University of Pittsburgh, Pennsylvania, USA
    Am J Gastroenterol 105:2276-86. 2010
    ..Our objective was to assess the efficacy and safety of a new formulation of pancrelipase (pancreatin) delayed-release 12,000-lipase unit capsules (CREON) in patients with EPI due to CP or PS...
  20. ncbi request reprint Acute pancreatitis: molecular biology update
    David C Whitcomb
    Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh and Pittsburgh VA Health Care System, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
    J Gastrointest Surg 7:940-2. 2003
  21. ncbi request reprint Mechanisms of disease: Advances in understanding the mechanisms leading to chronic pancreatitis
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA
    Nat Clin Pract Gastroenterol Hepatol 1:46-52. 2004
    ....
  22. ncbi request reprint Genetic predispositions to acute and chronic pancreatitis
    D C Whitcomb
    Department of Medicine, University of Pittsburgh, Pennsylvania, USA
    Med Clin North Am 84:531-47, vii. 2000
    ....
  23. ncbi request reprint Conference report for APA postgraduate course: clinical controversies in pancreatobiliary diseases
    David C Whitcomb
    Department of Medicine, University of Pittsburgh, Presbyterian University Hospital, Pittsburgh, PA 15213, USA
    Pancreas 31:218-20. 2005
  24. ncbi request reprint Pancreatitis as a risk for pancreatic cancer
    David C Whitcomb
    Department of Medicine, University of Pittsburgh, UPMC Presbyterian, Mezzanine Level, C Wing, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Gastroenterol Clin North Am 31:663-78. 2002
    ..g., long-standing HP), then screening for cancers must be considered. Inclusion in multicenter trials is recommended, and information on ongoing studies can be obtained through the office of Dr. Whitcomb, or as posted on www.pancreas.org...
  25. ncbi request reprint Conference report: Pittsburgh Pancreasfest 2005
    David C Whitcomb
    Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Pancreatology 6:138-40. 2006
  26. ncbi request reprint Evaluating disorders with a complex genetics basis. the future roles of meta-analysis and systems biology
    David C Whitcomb
    Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Dig Dis Sci 50:2195-202. 2005
    ..Instead, systems biology-based approaches should be developed to integrate multiple, focused, and mechanistic association studies with the goal of assisting in the risk assessment of patients on a person-by-person basis...
  27. ncbi request reprint Polygenetic traits in pancreatic disorders
    David C Whitcomb
    Department of Medicine, University of Pittsburgh, GI Administration, UPMC Presbyterian, Mezzanine Level 2, C Wing, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Endocrinol Metab Clin North Am 35:255-69, viii. 2006
    ..Instead, systems biology-based approaches should be developed to integrate multiple, focused, and mechanistic association studies, with the goal of assisting in the risk assessment of patients on a person-by-person basis...
  28. ncbi request reprint Clinical practice. Acute pancreatitis
    David C Whitcomb
    Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh, Pittsburgh, PA 15213, USA
    N Engl J Med 354:2142-50. 2006
  29. pmc Multicenter approach to recurrent acute and chronic pancreatitis in the United States: the North American Pancreatitis Study 2 (NAPS2)
    David C Whitcomb
    Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Pancreatology 8:520-31. 2008
    ..We developed the North American Pancreatitis Study 2 (NAPS2) to be sufficiently powered to understand the complex environmental, metabolic and genetic mechanisms underlying RAP and CP...
  30. ncbi request reprint Genetic polymorphisms in alcoholic pancreatitis
    David C Whitcomb
    Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Dig Dis 23:247-54. 2005
    ..Growing evidence suggests that environmental and possibly genetic cofactors must also be present to overcome the redundant mechanisms protecting the pancreas from pancreatitis and facilitating complete recovery...
  31. ncbi request reprint Chronic ethanol consumption induces gene expression of pancreatic monitor peptide, but not SPINK1/PSTI-56, in rats
    H S Li
    Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15216, USA
    Pancreas 23:117-24. 2001
    ..Because MP stimulates cholecystokinin release and cholecystokinin is an important stimulant of pancreatic secretion, the enhanced MP gene expression may contribute to pancreatic hypersecretion...
  32. ncbi request reprint Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis
    M C Gorry
    Department of Medicine, University of Pittsburgh, Pennsylvania, USA
    Gastroenterology 113:1063-8. 1997
    ..However, not all families studied have this mutation. The aim of this study was to determine the disease-causing mutation in kindreds with hereditary pancreatitis that lack the previously identified mutation...
  33. pmc Genetics of pancreatitis with a focus on the pancreatic ducts
    J Larusch
    Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Minerva Gastroenterol Dietol 58:299-308. 2012
    ..A simple duct cell model is given to illustration the relationship between CFTR, CASR, aquaporins, claudins, and SPINK1, and how they interact. The role of CFTR variants in pancreatic diseases is then discussed...
  34. ncbi request reprint A gene for hereditary pancreatitis maps to chromosome 7q35
    D C Whitcomb
    Department of Medicine, University of Pittsburgh, Pennsylvania 15261, USA
    Gastroenterology 110:1975-80. 1996
    ..A genetic linkage study was designed to identify the HP gene...
  35. pmc Expression and penetrance of the hereditary pancreatitis phenotype in monozygotic twins
    S T Amann
    Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL 32610 0214, USA
    Gut 48:542-7. 2001
    ....
  36. pmc Novel cationic trypsinogen (PRSS1) N29T and R122C mutations cause autosomal dominant hereditary pancreatitis
    R Pfutzer
    Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15101, USA
    Gut 50:271-2. 2002
    ..The N29T mutation may also enhance intrapancreatic trypsin activity as has been demonstrated in vitro. Identification of these new mutations requires special attention as commonly used detection methods may fail...
  37. ncbi request reprint The SPINK1 N34S mutation is not associated with Type 2 diabetes mellitus in a population of the USA
    A Schneider
    Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Diabet Med 22:744-8. 2005
    ..Therefore, we determined the frequency of SPINK1 N34S mutations in patients with Type 2 diabetes mellitus from the USA...
  38. pmc A 93 year old man with the PRSS1 R122H mutation, low SPINK1 expression, and no pancreatitis: insights into phenotypic non-penetrance
    A Khalid
    Division of Gastroenterology, Hepatology, and Nutrition, M2, C Wing, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
    Gut 55:728-31. 2006
    ..HP twins study suggests that modifier genes influence severity but not penetrance...
  39. ncbi request reprint PYY inhibits CCK-stimulated pancreatic secretion through the area postrema in unanesthetized rats
    X Deng
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, 3550 Terrace St, Pittsburgh, PA 15261, USA
    Am J Physiol Regul Integr Comp Physiol 281:R645-53. 2001
    ..9 vs. 68.9%) secretion in APX rats. Our findings demonstrate that PYY inhibits CCK-8-secretin-stimulated pancreatic secretion through an AP-dependent mechanism in sham-operated rats. The AP also contributes to basal pancreatic secretion...
  40. ncbi request reprint PYY potently inhibits pancreatic exocrine secretion mediated through CCK-secretin-stimulated pathways but not 2-DG-stimulated pathways in awake rats
    X Deng
    Department of Medicine, University of Pittsburgh, Pennsylvania 15261, USA
    Dig Dis Sci 46:156-65. 2001
    ..Therefore, the site of PYY's inhibitory action on pancreatic secretion appears to be primarily on the CCK-stimulated pathway at a site proximal to the convergence of the CCK and 2-DG pathways...
  41. ncbi request reprint Clinical characterization of patients with idiopathic chronic pancreatitis and SPINK1 Mutations
    A Schneider
    Department of Medicine, VA Pittsburgh Health Care System, Pittsburgh, PA 15101, USA
    Scand J Gastroenterol 39:903-4. 2004
  42. ncbi request reprint The area postrema lesions alter the inhibitory effects of peripherally infused pancreatic polypeptide on pancreatic secretion
    X Deng
    Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Room 571, Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    Brain Res 902:18-29. 2001
    ..p. injection of PP activates c-fos expression in DVC neurons. Thus, PP and PYY may regulate different components of the pancreatic secretory control system through unique pathways...
  43. ncbi request reprint The functional angiotensin converting enzyme gene I/D polymorphism does not alter susceptibility to chronic pancreatitis
    Nevin Oruc
    Department of Medicine, Division of Gastroenterology, and the Center for Genomic Sciences, University of Pittsburgh Pittsburgh, PA, USA
    JOP 5:457-63. 2004
    ..The pancreatic renin-angiotensin system plays a role in the development of pancreatic fibrosis and ACE inhibitors decrease pancreatic fibrosis in experimental models...
  44. ncbi request reprint Genetic polymorphisms in alcoholic pancreatitis
    Christoph Hanck
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, PUH, University of Pittsburgh, 571 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    Best Pract Res Clin Gastroenterol 17:613-23. 2003
    ..However, the major cofactor associated with alcoholic chronic pancreatitis is yet to be identified...
  45. ncbi request reprint SPINK1/PSTI polymorphisms act as disease modifiers in familial and idiopathic chronic pancreatitis
    R H Pfützer
    Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
    Gastroenterology 119:615-23. 2000
    ..Loss of trypsin inhibitor function may have similar effects. We investigated the prevalence of SPINK1 (PSTI) mutations in familial pancreatitis, idiopathic chronic pancreatitis, and controls...
  46. ncbi request reprint Genetic analysis of the glutathione s-transferase genes MGST1, GSTM3, GSTT1, and GSTM1 in patients with hereditary pancreatitis
    Alexander Schneider
    Department of Medicine, Division of Gastroenterology, University of Pittsburgh, 571 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15213, USA
    J Gastroenterol 39:783-7. 2004
    ..It has been suggested that oxidative stress contributes to pancreatic damage. The glutathione s-transferases (GSTs) represent major detoxification enzymes that protect cells from oxidative stress...
  47. pmc Pathways to injury in chronic pancreatitis: decoding the role of the high-risk SPINK1 N34S haplotype using meta-analysis
    Elie Aoun
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 3:e2003. 2008
    ..We tested this hypothesis by evaluating the differences in effect size of the high risk SPINK1 N34S haplotype on CP from multiple etiologies after combining clinical reports of SPINK1 N34S frequency using meta-analysis...
  48. ncbi request reprint Hereditary pancreatitis in North America: the Pittsburgh-Midwest Multi-Center Pancreatic Study Group Study
    S E Applebaum-Shapiro
    Department of Medicine, University of Pittsburgh, Center for Genomic Sciences, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Pancreatology 1:439-43. 2001
    ..The etiology of HP can be identified in a small majority of HP families through genetic testing. However, family history alone is not a good predictor of finding a mutation in the cationic trypsinogen (PRSS1) gene...
  49. ncbi request reprint Hereditary pancreatitis amlodipine trial: a pilot study of a calcium-channel blocker in hereditary pancreatitis
    Veronique D Morinville
    Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Pancreas 35:308-12. 2007
    ..Because of the potential importance of hyperstimulation in triggering episodes of AP in HP, we designed a pilot study to evaluate the safety and potential benefit of CCB use in HP...
  50. doi request reprint Low serum adiponectin levels are associated with systemic organ failure in acute pancreatitis
    Arun Sharma
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Pancreas 38:907-12. 2009
    ..We tested the hypothesis that serum adiponectin, the primary anti-inflammatory adipokine, is associated with functional polymorphisms in the adiponectin gene (ADIPOQ) and inversely associated with SAP...
  51. ncbi request reprint Lessons from hereditary pancreatitis
    D C Whitcomb
    Department of Medicine, University of Pittsburgh and the Veterans Affairs Pittsburgh Health Care System, PA, USA
    Croat Med J 42:484-7. 2001
    ..This newly acquired knowledge is setting the stage for new preventive and management strategies for hereditary and sporadic acute and chronic pancreatitis...
  52. ncbi request reprint Motivations and concerns of patients with access to genetic testing for hereditary pancreatitis
    S E Applebaum-Shapiro
    Center for Genomic Sciences, University of Pittsburgh, Pennsylvania 15261, USA
    Am J Gastroenterol 96:1610-7. 2001
    ..These results suggest that a mechanism to disclose results to research participants should be considered, and effective ways to protect at-risk individuals from insurance discrimination must remain a genetics health care priority...
  53. doi request reprint SPINK1 N34S is strongly associated with recurrent acute pancreatitis but is not a risk factor for the first or sentinel acute pancreatitis event
    Elie Aoun
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
    Am J Gastroenterol 105:446-51. 2010
    ..Our aim was to study the prevalence of the SPINK1 N34S polymorphism in patients with sentinel and recurrent AP (RAP)...
  54. ncbi request reprint Predictors of severity and necrosis in acute pancreatitis
    Georgios I Papachristou
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Gastroenterol Clin North Am 33:871-90. 2004
    ..Novel conceptions and approaches, such as identification of genetic polymorphisms that predispose to severe course and complications of AP or other approaches are needed for a quantum step forward...
  55. ncbi request reprint Keratin 8 mutations are not associated with familial, sporadic and alcoholic pancreatitis in a population from the United States
    Alexander Schneider
    Department of Medicine, Division of Gastroenterology, University of Pittsburgh, Pittsburgh, PA, USA
    Pancreatology 6:103-8. 2006
    ..We determined whether mutations in the keratin 8 gene are associated with familial, sporadic and alcoholic recurrent acute or chronic pancreatitis in a population from the United States...
  56. ncbi request reprint Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene
    D C Whitcomb
    Dept of Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA
    Nat Genet 14:141-5. 1996
    ..Cleavage at this site is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis...
  57. ncbi request reprint Distribution of pancreatic polypeptide receptors in the rat brain
    D C Whitcomb
    Department of Medicine, University of Pittsburgh, PA 15261, USA
    Brain Res 760:137-49. 1997
    ..We speculate, based on the patterns of binding in the olfactory and limbic systems, that PP receptors might be involved in positive reinforcement of ingestion behavioral as well as modulation of gastrointestinal function...
  58. ncbi request reprint Human pancreatic digestive enzymes
    David C Whitcomb
    Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Dig Dis Sci 52:1-17. 2007
    ..This report updates our understanding of human pancreatic digestive enzymes with a focus on new insights into the biology of human proteases, lipases and amylases...
  59. ncbi request reprint SPINK1/PSTI mutations are associated with tropical pancreatitis and type II diabetes mellitus in Bangladesh
    Alexander Schneider
    Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
    Gastroenterology 123:1026-30. 2002
    ..A more extensive investigation of patients with pancreatic diseases in Bangladesh, including non-insulin-dependent diabetes mellitus, was undertaken...
  60. ncbi request reprint Alcohol-associated pancreatitis
    Dhiraj Yadav
    Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Gastroenterol Clin North Am 36:219-38, vii. 2007
    ..Newer developments in the understanding of complex disorders allow clinicians to understand better the role of cofactors and interactions between known and yet unknown environmental and genetic factors in causing alcoholic pancreatitis...
  61. ncbi request reprint Risk and markers of severe acute pancreatitis
    Georgios I Papachristou
    Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Gastroenterol Clin North Am 36:277-96, viii. 2007
    ....
  62. ncbi request reprint Motion--genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: arguments for the motion
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pennsylvania, USA
    Can J Gastroenterol 17:47-52. 2003
    ..In the future, increased knowledge of the myriad genetic causes of pancreatitis, as well as advances in the diagnosis and treatment of early chronic pancreatitis, should enhance the utility of genetic testing...
  63. doi request reprint Comparison of BISAP, Ranson's, APACHE-II, and CTSI scores in predicting organ failure, complications, and mortality in acute pancreatitis
    Georgios I Papachristou
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
    Am J Gastroenterol 105:435-41; quiz 442. 2010
    ....
  64. doi request reprint Current management and novel insights in acute pancreatitis
    Venkata Muddana
    Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, PA 15219, USA
    Expert Rev Gastroenterol Hepatol 3:435-44. 2009
    ..The lack of scientific advancements in the management of AP reflects the limited understanding of the early pathogenetic mechanisms and our moderate-to-poor ability to predict severe course at the time of admission...
  65. doi request reprint Alcohol consumption, cigarette smoking, and the risk of recurrent acute and chronic pancreatitis
    Dhiraj Yadav
    Department of Medicine, University of Pittsburgh, 3708 Fifth Ave, Pittsburgh, PA 15213, USA
    Arch Intern Med 169:1035-45. 2009
    ..We examined the current prevalence of alcohol use and smoking and their association with RAP and CP in patients evaluated at US referral centers...
  66. doi request reprint Epidermal growth factor serum levels and the 61 G/A polymorphism in patients with acute pancreatitis
    Georgios I Papachristou
    Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Presbyterian, M2 C Wing, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Dig Dis Sci 55:2676-80. 2010
    ..In animal models, EGF protects against pancreatic injury and prevents septic complications. The role of EGF in human AP is unknown...
  67. ncbi request reprint Limited contribution of the SPINK1 N34S mutation to the risk and severity of alcoholic chronic pancreatitis: a report from the United States
    Alexander Schneider
    Department of Medicine, Division of Gastroenterology, Center for Genomic Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Dig Dis Sci 48:1110-5. 2003
    ..The N34S mutation is uncommon in patients with alcoholic chronic pancreatitis in the United States; its prevalence is similar to other countries and appears not to alter the onset or the severity of alcoholic chronic pancreatitis...
  68. ncbi request reprint Obesity increases the severity of acute pancreatitis: performance of APACHE-O score and correlation with the inflammatory response
    Georgios I Papachristou
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Pancreatology 6:279-85. 2006
    ..Obese patients appear to be at risk for complications of acute pancreatitis (AP). APACHE-O score has been suggested to improve APACHE-II accuracy in predicting severe outcome in AP...
  69. ncbi request reprint Genetic issues in pediatric pancreatitis
    Leena Kandula
    Department of Pediatrics, Children s Hospital of Pittsburgh, 3705 Fifth Avenue, 2nd Floor DeSoto Bldg, Pittsburgh, PA 15213, USA
    Curr Gastroenterol Rep 8:248-53. 2006
    ..These findings, along with the advances in cell biology, have contributed to a better understanding of the pathophysiology of pancreatic diseases...
  70. ncbi request reprint Rat mitochondrial ATP synthase ATP5G3: cloning and upregulation in pancreas after chronic ethanol feeding
    H S Li
    Department of Medicine, Center for Genomic Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
    Physiol Genomics 6:91-8. 2001
    ..The cellular response to mitochondrial damage and metabolic stress may reflect an adaptive process for mitochondrial repair in pancreatic acinar cells during chronic ethanol ingestion...
  71. ncbi request reprint Obesity and the risk of severe acute pancreatitis
    A C Evans
    College of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Minerva Gastroenterol Dietol 56:169-79. 2010
    ....
  72. ncbi request reprint Area postrema lesion alters the effects of peptide YY on 2-DG-stimulated pancreatic exocrine secretion
    X Deng
    Department of Medicine, University of Pittsburgh, Pennsylvania 15261, USA
    Dig Dis Sci 46:2460-9. 2001
    ....
  73. ncbi request reprint Is the monocyte chemotactic protein-1 -2518 G allele a risk factor for severe acute pancreatitis?
    Georgios I Papachristou
    Department of Medicine, University of Pittsburgh, Pennsylvania 15213, USA
    Clin Gastroenterol Hepatol 3:475-81. 2005
    ..Our aim was to determine whether the MCP-1 -2518 A/G polymorphism affects the severity of AP...
  74. ncbi request reprint Hereditary, familial, and idiopathic chronic pancreatitis are not associated with polymorphisms in the tumor necrosis factor alpha (TNF-alpha) promoter region or the TNF receptor 1 (TNFR1) gene
    Alexander Schneider
    Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Genet Med 5:120-5. 2003
    ..Genetic alterations that are associated with acute and chronic pancreatitis remain to be identified...
  75. ncbi request reprint Inflammatory markers of disease severity in acute pancreatitis
    Georgios I Papachristou
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Clin Lab Med 25:17-37. 2005
    ..Novel conceptions and approaches, such as identification of genetic polymorphisms that predispose to severe course and complications of AP, are needed for a quantum step forward...
  76. doi request reprint Elevated serum creatinine as a marker of pancreatic necrosis in acute pancreatitis
    Venkata Muddana
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, UPMC Presbyterian Hospital, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Am J Gastroenterol 104:164-70. 2009
    ..This study focuses on the association between routine laboratory tests and the development of pancreatic necrosis in patients with acute pancreatitis...
  77. doi request reprint Inflammation and pancreatic cancer: an evidence-based review
    Julia B Greer
    University of Pittsburgh School of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Medical Arts Building, 4th Floor, Office 400 5, 3708 5th Ave, Pittsburgh, PA 15213, United States
    Curr Opin Pharmacol 9:411-8. 2009
    ..Each risk factor is linked by the fact that the inflammatory state significantly drives its pathology. This article will outline how inflammatory mechanisms are etiologically linked to pancreatic adenocarcinoma...
  78. ncbi request reprint Serum proteomic patterns as a predictor of severity in acute pancreatitis
    Georgios I Papachristou
    Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Cancer Institute Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Pancreatology 7:317-24. 2007
    ....
  79. ncbi request reprint Functional polymorphisms of the GSTT-1 gene do not predict the severity of acute pancreatitis in the United States
    Yasser M Bhat
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Pancreatology 7:180-6. 2007
    ..Our aim was to determine whether the same GSTT-1 polymorphism affects the severity of AP in a population from Pittsburgh, Pa., USA...
  80. ncbi request reprint Genetic counseling for nonsyndromic pancreatitis
    Erin N Fink
    Department of Medicine, University of Pittsburgh, 1218 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15213, USA
    Gastroenterol Clin North Am 36:325-33, ix. 2007
    ..This article focuses on the approach to genetic counseling for pancreatitis and implications of recent advances...
  81. pmc Association between calcium sensing receptor gene polymorphisms and chronic pancreatitis in a US population: role of serine protease inhibitor Kazal 1type and alcohol
    Venkata Muddana
    Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh PA 15213, USA
    World J Gastroenterol 14:4486-91. 2008
    ....
  82. pmc Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism
    Kay L Pogue-Geile
    Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
    PLoS Med 3:e516. 2006
    ..In this study, our goal was to discover the identity of the familial pancreatic cancer gene on 4q32 and determine the function of that gene...
  83. ncbi request reprint Alcoholic pancreatitis
    Christoph Hanck
    Department of Medicine, University of Pittsburgh, UPMC Presbyterian, Mezzanine Level C Wing, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Gastroenterol Clin North Am 33:751-65. 2004
    ..If alcohol-associated pancreatitis is detected, then limitation of pancreatic damage, limitation of progression, or preventative intervention should become the major concern...
  84. doi request reprint The role of alcohol and smoking in pancreatitis
    Dhiraj Yadav
    Department of Medicine, University of Pittsburgh, Room 401 4, 3708 Fifth Avenue, Pittsburgh, PA 15213, USA
    Nat Rev Gastroenterol Hepatol 7:131-45. 2010
    ..In humans, aggressive interventional counseling against alcohol use may reduce the frequency of recurrent attacks of disease and smoking cessation may help to slow the progression of acute to chronic pancreatitis...
  85. pmc Chronic alcohol consumption accelerates fibrosis in response to cerulein-induced pancreatitis in rats
    Xiaoying Deng
    Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Am J Pathol 166:93-106. 2005
    ..Pancreatic fibrosis develops after repeated episodes of AP and is potentiated by alcohol. Expression of fibrosis-associated genes was associated with expression of anti-inflammatory cytokines in alcohol-fed rats...
  86. doi request reprint MUTYH exon 7 and 13 mutations associated with colorectal cancer (MAP syndrome) are not commonly associated with sporadic pancreatic cancer
    Lauren M Smith
    School of Arts and Sciences, University of Pittsburgh, and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
    Pancreatology 9:793-6. 2009
    ..The purpose of this study was to determine if a similar association exists between exon 7 and 13 MUTYH mutations and pancreatic cancer...
  87. doi request reprint Serum immunoglobulin G fraction 4 levels in pancreatic cancer: elevations not associated with autoimmune pancreatitis
    Amit Raina
    Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    Arch Pathol Lab Med 132:48-53. 2008
    ..A previous Japanese study reported that serum IgG4 greater than 135 mg/dL was 97% specific and 95% sensitive in predicting autoimmune pancreatitis...
  88. ncbi request reprint Hereditary pancreatitis: a model for inflammatory diseases of the pancreas
    Alexander Schneider
    Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh, Pittsburgh, PA 15101, USA
    Best Pract Res Clin Gastroenterol 16:347-63. 2002
    ..Finally, the major independent theories on development of chronic pancreatitis are reviewed with respect to the SAPE hypothesis of chronic pancreatitis pathogenesis...
  89. ncbi request reprint Challenges of examining complex genetic disorders like GERD
    Susan R Orenstein
    University of Pittsburgh School of Medicine, Pittsburgh, USA
    J Pediatr Gastroenterol Nutr 41:S17-9. 2005
  90. pmc Role of BRCA1 and BRCA2 mutations in pancreatic cancer
    Julia B Greer
    Department of Medicine, University of Pittsburgh, Division of Gastroenterology, Hepatology and Nutrition, Presbyterian University Hospital, Mezzanine 2, C Wing, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213, USA
    Gut 56:601-5. 2007
    ..We are just beginning to elucidate what these factors are...
  91. ncbi request reprint Acute pancreatitis in association with Campylobacter jejuni-associated diarrhea in a 15-year-old with CFTR mutations: is there a link?
    Leena Kandula
    Department of Pediatrics, University of Pittsburgh, Children s Hospital of Pittsburgh, PA 15213, USA
    JOP 7:482-5. 2006
    ..For instance, studies show that mutations in the cystic fibrosis transmembrane conductance regulator gene increase the susceptibility for acute and chronic pancreatitis...
  92. ncbi request reprint Transforming growth factor-beta1, interleukin-10 and interferon-gamma cytokine polymorphisms in patients with hereditary, familial and sporadic chronic pancreatitis
    Alexander Schneider
    Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15101, USA
    Pancreatology 4:490-4. 2004
    ..Cytokines participate in the immunological progression of pancreatic inflammation and may play an important role in the development of pancreatic fibrosis...
  93. ncbi request reprint Rapid evolution from the first episode of acute pancreatitis to chronic pancreatitis in human subjects
    Elie Aoun
    Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    JOP 8:573-8. 2007
    ..The sentinel acute pancreatitis event hypothesis suggests that an initial episode of acute pancreatitis is the first step in a complicated series of events ultimately leading to chronic pancreatitis...
  94. ncbi request reprint Serology in autoimmune pancreatitis
    A Raina
    University of Pittsburgh School of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Pittsburgh, PA 15213, USA
    Minerva Gastroenterol Dietol 54:375-87. 2008
    ..At the current time, elevations of IgG4 to greater than 280 mg/dL remain the most reliable and reproducible indicator that a patient has AIP...
  95. ncbi request reprint The MCP-1 -2518 A/G polymorphism is not a susceptibility factor for chronic pancreatitis
    David A Sass
    Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Pancreatology 6:297-300. 2006
    ..Genetic factors influence susceptibility and modify progression. The monocyte chemotactic protein-1 (MCP-1) -2518 G allele, which modifies the severity of acute pancreatitis, was investigated as a susceptibility factor for CP...
  96. doi request reprint Diagnostic accuracy of interleukin-6 and interleukin-8 in predicting severe acute pancreatitis: a meta-analysis
    Elie Aoun
    Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    Pancreatology 9:777-85. 2009
    ..We conducted a meta-analysis to assess the accuracy of IL-6 and IL-8 at predicting SAP...
  97. ncbi request reprint Molecular and genetic aspects of gastrointestinal and pancreatic disease
    David C Whitcomb
    Division of Gastroenterology, Hepatology and Nutrition, Director, Center for Genomic Sciences, University of Pittsburgh, UPMC Presbyterian, M2 C Wing, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Clin Lab Med 25:xi-xii. 2005
  98. ncbi request reprint Clinical and genetic characteristics of hereditary pancreatitis in Europe
    Nathan Howes
    Department of Surgery, University of Liverpool, United Kingdom
    Clin Gastroenterol Hepatol 2:252-61. 2004
    ..Hereditary pancreatitis is an autosomal dominant disease that is mostly caused by cationic trypsinogen (PRSS1) gene mutations. The aim was to determine phenotype-genotype correlations of families in Europe...
  99. ncbi request reprint Acute pancreatitis in children
    John R DeBanto
    Division of Digestive Diseases and Nutrition, University of Kentucky, Lexington, USA
    Am J Gastroenterol 97:1726-31. 2002
    ..Our intent was to evaluate the performance of existing scoring systems in children, to develop a system for children, and to examine the etiology of acute pancreatitis in children...
  100. pmc SPINK1 is a susceptibility gene for fibrocalculous pancreatic diabetes in subjects from the Indian subcontinent
    Zahid Hassan
    Barts and The London Queen Mary s School of Medicine and Dentistry, London, United Kingdom
    Am J Hum Genet 71:964-8. 2002
    ..02 compared with the ethnically matched control group). These results suggest that the N34S variant of SPINK1 is a susceptibility gene for FCPD in the Indian subcontinent, although, by itself, it is not sufficient to cause disease...
  101. ncbi request reprint Analysis of tumor necrosis factor-alpha, transforming growth factor-beta 1, interleukin-10, and interferon-gamma polymorphisms in patients with alcoholic chronic pancreatitis
    Alexander Schneider
    Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Alcohol 32:19-24. 2004
    ..05). We did not find an association between the different genotypes and the clinical course of the disease. Therefore, we assume that these genetic variants do not play a dominant role in alcoholic chronic pancreatitis...

Research Grants22

  1. North American Pancreatitis Study 2 (NAPS2)
    David Whitcomb; Fiscal Year: 2006
    ..The results of these studies may result in the development new diagnostic tools that can be applied at the onset of symptoms, and rational therapy to prevent the development of those pancreatic diseases that we cannot currently cure. ..
  2. MOLECULAR GENETICS OF HEREDITARY PANCREATITIS
    David Whitcomb; Fiscal Year: 2007
    ..The HP and familial pancreatitis studies are especially important because of the statistical power of family studies and the ability to detect modifier genes in a uniform background of susceptibility factors. ..
  3. Digestive Diseases Training Program
    David Whitcomb; Fiscal Year: 2007
    ..Postdoctoral graduates will be prepared to compete for independent funding and entry-level faculty positions in academic medicine ..
  4. NAPS2 Continuation - Genome-Wide Association Study of Pancreatitis
    David Whitcomb; Fiscal Year: 2009
    ..Knowledge of the genetic basis of pancreatitis will lead to new treatments, and help remove the stigma that chronic pancreatitis is only a disease of drunkards. ..
  5. NAPS2-AS: Race Dependent Risk for Pancreatitis
    David C Whitcomb; Fiscal Year: 2010
    ....
  6. NAPS2 Continuation - Genome-Wide Association Study of Pancreatitis
    David C Whitcomb; Fiscal Year: 2010
    ..Knowledge of the genetic basis of pancreatitis will lead to new treatments, and help remove the stigma that chronic pancreatitis is only a disease of drunkards. ..
  7. MOLECULAR GENETICS OF HEREDITARY PANCREATITIS
    David Whitcomb; Fiscal Year: 2002
    ..Answering this question may provide insight into the pathophysiology of acute and chronic pancreatitis and identify targets for new therapies, and help identify individuals at risk through genetic testing. ..
  8. 14th Internatinal Symposium on Inherited Diseases
    David Whitcomb; Fiscal Year: 2004
    ..The format, venue, and content are designed to maximize participation, education, translation and implementation of the key elements of the many new findings in the genetics of the pancreas. ..
  9. NAPS2 Continuation - Genome-Wide Association Study of Pancreatitis
    David Whitcomb; Fiscal Year: 2009
    ..Knowledge of the genetic basis of pancreatitis will lead to new treatments, and help remove the stigma that chronic pancreatitis is only a disease of drunkards. ..