Joel E Lavine

Summary

Affiliation: University of California
Country: USA

Publications

  1. ncbi request reprint Nonalcoholic fatty liver disease in the pediatric population
    Joel E Lavine
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego Medical Center and Children s Hospital, 200 W Arbor Drive, San Diego, CA 92103 8450, USA
    Clin Liver Dis 8:549-58, viii-ix. 2004
  2. pmc Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis
    Heather M Patton
    Division of Gastroenterology, University of California, San Diego, San Diego, California 92103, USA
    Gastroenterology 135:1961-1971.e2. 2008
  3. pmc Physical activity recommendations, exercise intensity, and histological severity of nonalcoholic fatty liver disease
    Kristin D Kistler
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego, California 92103, USA
    Am J Gastroenterol 106:460-8; quiz 469. 2011
  4. pmc Association between puberty and features of nonalcoholic fatty liver disease
    Ayako Suzuki
    Division of Gastroenterology, Duke University, Durham, NC 27710, USA
    Clin Gastroenterol Hepatol 10:786-94. 2012
  5. pmc Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial
    Joel E Lavine
    Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Columbia University, New York, New York, USA
    JAMA 305:1659-68. 2011
  6. pmc Nonalcoholic fatty liver disease: MR imaging of liver proton density fat fraction to assess hepatic steatosis
    An Tang
    Liver Imaging Group, Department of Radiology, University of California San Diego, 408 Dickinson St, San Diego, CA 92103 8226, USA
    Radiology 267:422-31. 2013
  7. pmc Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease
    Amy G Shah
    Division of Gastroenterology, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
    Clin Gastroenterol Hepatol 7:1104-12. 2009
  8. pmc Effect of PRESS and STEAM sequences on magnetic resonance spectroscopic liver fat quantification
    Gavin Hamilton
    Department of Radiology, University of California, San Diego, San Diego, California 92103 8226, USA
    J Magn Reson Imaging 30:145-52. 2009
  9. pmc Histological abnormalities in children with nonalcoholic fatty liver disease and normal or mildly elevated alanine aminotransferase levels
    Jean P Molleston
    Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Indiana University School of Medicine, Indianapolis, IN Electronic address
    J Pediatr 164:707-713.e3. 2014
  10. pmc PedsQL™ Cognitive Functioning Scale in pediatric liver transplant recipients: feasibility, reliability, and validity
    James W Varni
    Department of Pediatrics, College of Medicine, Department of Landscape Architecture and Urban Planning, College of Architecture, Texas A and M University, 3137 TAMU, College Station, TX 77843 3137, USA
    Qual Life Res 20:913-21. 2011

Detail Information

Publications51

  1. ncbi request reprint Nonalcoholic fatty liver disease in the pediatric population
    Joel E Lavine
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego Medical Center and Children s Hospital, 200 W Arbor Drive, San Diego, CA 92103 8450, USA
    Clin Liver Dis 8:549-58, viii-ix. 2004
    ..Important differences between pediatric and adult fatty liver disease are highlighted...
  2. pmc Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis
    Heather M Patton
    Division of Gastroenterology, University of California, San Diego, San Diego, California 92103, USA
    Gastroenterology 135:1961-1971.e2. 2008
    ..Noninvasive means to discriminate between NAFLD and nonalcoholic steatohepatitis (NASH) might diminish the requirement for liver biopsy or predict those at increased risk for progression...
  3. pmc Physical activity recommendations, exercise intensity, and histological severity of nonalcoholic fatty liver disease
    Kristin D Kistler
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego, California 92103, USA
    Am J Gastroenterol 106:460-8; quiz 469. 2011
    ..Factors that determine disease severity in nonalcoholic fatty liver disease (NAFLD) are unclear, but exercise is a recommended treatment. We evaluated the association between physical activity intensity and histological severity of NAFLD...
  4. pmc Association between puberty and features of nonalcoholic fatty liver disease
    Ayako Suzuki
    Division of Gastroenterology, Duke University, Durham, NC 27710, USA
    Clin Gastroenterol Hepatol 10:786-94. 2012
    ..Physiological changes that occur during puberty might affect pathologic features of nonalcoholic fatty liver disease (NAFLD). We investigated associations between pubertal development and clinical and histopathologic features of NAFLD...
  5. pmc Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial
    Joel E Lavine
    Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Columbia University, New York, New York, USA
    JAMA 305:1659-68. 2011
    ..Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in US children and adolescents and can present with advanced fibrosis or nonalcoholic steatohepatitis (NASH). No treatment has been established...
  6. pmc Nonalcoholic fatty liver disease: MR imaging of liver proton density fat fraction to assess hepatic steatosis
    An Tang
    Liver Imaging Group, Department of Radiology, University of California San Diego, 408 Dickinson St, San Diego, CA 92103 8226, USA
    Radiology 267:422-31. 2013
    ....
  7. pmc Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease
    Amy G Shah
    Division of Gastroenterology, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
    Clin Gastroenterol Hepatol 7:1104-12. 2009
    ..We compared the performance of the FIB4 index (based on age, aspartate aminotransferase [AST] and alanine aminotransferase [ALT] levels, and platelet counts) with 6 other non-invasive markers of fibrosis in patients with NAFLD...
  8. pmc Effect of PRESS and STEAM sequences on magnetic resonance spectroscopic liver fat quantification
    Gavin Hamilton
    Department of Radiology, University of California, San Diego, San Diego, California 92103 8226, USA
    J Magn Reson Imaging 30:145-52. 2009
    ..To compare PRESS and STEAM MR spectroscopy for assessment of liver fat in human subjects...
  9. pmc Histological abnormalities in children with nonalcoholic fatty liver disease and normal or mildly elevated alanine aminotransferase levels
    Jean P Molleston
    Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Indiana University School of Medicine, Indianapolis, IN Electronic address
    J Pediatr 164:707-713.e3. 2014
    ....
  10. pmc PedsQL™ Cognitive Functioning Scale in pediatric liver transplant recipients: feasibility, reliability, and validity
    James W Varni
    Department of Pediatrics, College of Medicine, Department of Landscape Architecture and Urban Planning, College of Architecture, Texas A and M University, 3137 TAMU, College Station, TX 77843 3137, USA
    Qual Life Res 20:913-21. 2011
    ..The objective of the present study was to determine the feasibility, reliability, and validity of the PedsQL™ Cognitive Functioning Scale in pediatric liver transplant recipients...
  11. pmc Estimation of hepatic proton-density fat fraction by using MR imaging at 3.0 T
    Takeshi Yokoo
    Department of Radiology, University of California at San Diego, 408 Dickinson St, San Diego, CA 92103 8592, USA
    Radiology 258:749-59. 2011
    ..To compare the accuracy of several magnetic resonance (MR) imaging-based methods for hepatic proton-density fat fraction (FF) estimation at 3.0 T, with spectroscopy as the reference technique...
  12. pmc Nonalcoholic fatty liver disease: diagnostic and fat-grading accuracy of low-flip-angle multiecho gradient-recalled-echo MR imaging at 1.5 T
    Takeshi Yokoo
    Department of Radiology, University of California, San Diego Medical Center, University of California at San Diego, MR3 Laboratory, 408 Dickinson St, San Diego, CA 92103 8226, USA
    Radiology 251:67-76. 2009
    ....
  13. pmc Liver biopsy in modern clinical practice: a pediatric point-of-view
    Nadia Ovchinsky
    Department of Pediatrics, Morgan Stanley Children s Hospital of New York, NY, USA
    Adv Anat Pathol 19:250-62. 2012
    ..This review presents specific indications, considerations, methods, complications, contraindications, and alternatives for pediatric liver biopsy...
  14. pmc Heritability of nonalcoholic fatty liver disease
    Jeffrey B Schwimmer
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, California 92103, USA
    Gastroenterology 136:1585-92. 2009
    ..Therefore, a familial aggregation study was performed to test the hypothesis that NAFLD is highly heritable...
  15. pmc Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease
    Manal F Abdelmalek
    Division of Gastroenterology, Duke University, Durham, NC 27710, USA
    Hepatology 51:1961-71. 2010
    ..05 for each). In older adults (age > or = 48 years), daily fructose consumption was associated with increased hepatic inflammation (P < 0.05) and hepatocyte ballooning (P = 0.05)...
  16. pmc Association between metabolic syndrome and liver histology among children with nonalcoholic Fatty liver disease
    Heather M Patton
    Departments of Medicine and Pediatrics, University of California, San Diego, San Diego, California, USA
    Am J Gastroenterol 105:2093-102. 2010
    ..We sought to determine whether MetS or its component features are associated with specific histological features or severity of NAFLD...
  17. ncbi request reprint Pediatric nonalcoholic fatty liver disease: a critical appraisal of current data and implications for future research
    Heather M Patton
    Division of Gastroenterology, Department of Medicine, University of California, San Diego, CA, USA
    J Pediatr Gastroenterol Nutr 43:413-27. 2006
    ..A large, multicenter trial of vitamin E and metformin is underway as part of the NASH clinical research network...
  18. pmc Advances in pediatric nonalcoholic fatty liver disease
    Rohit Loomba
    Division of Gastroenterology, Department of Medicine, University of California at San Diego and Rady Children s Hospital, San Diego, CA, USA
    Hepatology 50:1282-93. 2009
    ..Targeted therapies to improve liver histology and metabolic abnormalities associated with fatty liver are needed. Currently, randomized-controlled trials are underway in the pediatric population to define pharmacologic therapy for NAFLD...
  19. pmc Diagnosis and treatment of pediatric nonalcoholic steatohepatitis and the implications for bariatric surgery
    Perrie E Pardee
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California San Diego, and Rady Children s Hospital, San Diego, California CA 92103 8450, USA
    Semin Pediatr Surg 18:144-51. 2009
    ..Several clinical trials for NAFLD are in progress; however, clinical trials focusing on NASH are needed. Heightened physician awareness of NAFLD, NASH, and associated risk factors is important to identify and treat affected children...
  20. ncbi request reprint Prevalence of fatty liver in children and adolescents
    Jeffrey B Schwimmer
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, 200 West Arbor Dr, San Diego, CA 92103 8450, USA
    Pediatrics 118:1388-93. 2006
    ..Fatty liver disease is diagnosed increasingly in children, but the prevalence remains unknown. We sought to determine the prevalence of pediatric fatty liver as diagnosed by histology in a population-based sample...
  21. ncbi request reprint Influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents
    Jeffrey B Schwimmer
    Division of Gastroenterology, Hepatology, and Nutrition, University of California, 200 W Arbor Dr, San Diego, CA 92103 8450, USA
    Pediatrics 115:e561-5. 2005
    ..Obesity and insulin resistance are major established risk factors for NAFLD. The role of gender, race, and ethnicity on the prevalence of fatty liver in obese children is unknown...
  22. doi request reprint A critical appraisal of advances in pediatric nonalcoholic Fatty liver disease
    Nadia Ovchinsky
    Department of Pediatrics, Columbia College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Semin Liver Dis 32:317-24. 2012
    ..In this review, the authors provide an overview of current concepts in epidemiology, histologic features, diagnosis, pathophysiology, genetic risk factors, and treatment of NAFLD in children...
  23. pmc Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease
    Jeffrey B Schwimmer
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego, 200 W Arbor Dr, San Diego, CA 92103 8450, USA
    Circulation 118:277-83. 2008
    ..The objective of this study was to determine the association between NAFLD and the presence of metabolic syndrome in overweight and obese children...
  24. doi request reprint Hepatic, cardiovascular, and endocrine outcomes of the histological subphenotypes of nonalcoholic fatty liver disease
    Eitan Rubinstein
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego, Rady Children s Hospital, San Diego, California 92103 8450, USA
    Semin Liver Dis 28:380-5. 2008
    ....
  25. ncbi request reprint Histopathology of pediatric nonalcoholic fatty liver disease
    Jeffrey B Schwimmer
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California San Diego School of Medicine, San Diego, CA 92103 8450, USA
    Hepatology 42:641-9. 2005
    ..NASH subtypes should be considered when interpreting liver biopsies and planning studies of the pathophysiology, genetics, natural history, or response to treatment in pediatric NAFLD...
  26. doi request reprint Prevalence of Prediabetes and Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease
    Kimberly P Newton
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California San Diego School of Medicine, La Jolla2Department of Gastroenterology, Rady Children s Hospital, San Diego, California
    JAMA Pediatr 170:e161971. 2016
    ..In adults, NAFLD is also associated with type 2 diabetes. To our knowledge, the prevalence of type 2 diabetes in children with NAFLD is unknown...
  27. pmc Serum aminotransferase levels are associated with markers of hypoxia in patients with obstructive sleep apnea
    Daniel Norman
    Department of Pulmonary and Critical Care Medicine, University of California at San Diego, San Diego, CA 92103 8383, USA
    Sleep 31:121-6. 2008
    ....
  28. pmc Acetaminophen pharmacokinetics in children with nonalcoholic fatty liver disease
    Nicole J Barshop
    Department of Pediatrics, University of California, San Diego, USA
    J Pediatr Gastroenterol Nutr 52:198-202. 2011
    ..The aim of the study was to evaluate UDP-glucuronyltransferase activity and the pharmacokinetics of a single oral dose of acetaminophen (APAP) in children with nonalcoholic fatty liver disease (NAFLD)...
  29. ncbi request reprint Lumen and the liver--together again in NASHville
    Jeffrey B Schwimmer
    Department of Pediatrics, University of California, San Diego, USA
    J Pediatr Gastroenterol Nutr 37:523-4. 2003
  30. ncbi request reprint Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease
    Jeffrey B Schwimmer
    Joint Program in Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Family and Preventive Medicine, Department of Pathology, The School of Medicine, University of California San Diego, 200 West Arbor Drive, San Diego, CA 92103, USA
    J Pediatr 143:500-5. 2003
    ..To describe the clinical characteristics of nonalcoholic fatty liver disease (NAFLD) in children, including insulin resistance, and to test for correlation with liver pathology...
  31. pmc Symptoms and quality of life in obese children and adolescents with non-alcoholic fatty liver disease
    K D Kistler
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego, La Jolla, CA 92103, USA
    Aliment Pharmacol Ther 31:396-406. 2010
    ..Data on the quality of life (QOL) of children with non-alcoholic fatty liver disease (NAFLD) are needed to estimate the true burden of illness in children with NAFLD...
  32. pmc Placebo in nonalcoholic steatohepatitis: insight into natural history and implications for future clinical trials
    Rohit Loomba
    Liver Diseases Branch, National Institute of Diabetes and Digestive Diseases, National Institutes of Health, Bethesda, Maryland, USA
    Clin Gastroenterol Hepatol 6:1243-8. 2008
    ..The aim of our study was to assess the biochemical and histologic changes seen in the placebo arm of the randomized, placebo-controlled trials in adult patients with NASH...
  33. pmc Feasibility of and agreement between MR imaging and spectroscopic estimation of hepatic proton density fat fraction in children with known or suspected nonalcoholic fatty liver disease
    Emil Achmad
    Liver Imaging Group, Department of Radiology, School of Medicine, University of California, San Diego, San Diego, CA, USA
    Abdom Imaging 40:3084-90. 2015
    ....
  34. pmc Characterization and outcomes of young infants with acute liver failure
    Shikha S Sundaram
    Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, The Children s Hospital, University of Colorado School of Medicine, Aurora, CO, USA
    J Pediatr 159:813-818.e1. 2011
    ..To characterize infants aged ≤ 90 days enrolled in an international, multicenter, prospective registry of children aged < 18 years with acute liver failure (ALF)...
  35. pmc In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but Does Not Reduce Disease Activity Scores
    Jeffrey B Schwimmer
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California Department of Gastroenterology, Rady Children s Hospital, San Diego, California Electronic address
    Gastroenterology 151:1141-1154.e9. 2016
    ..We performed a randomized controlled trial to determine whether 52 weeks of cysteamine bitartrate delayed release (CBDR) reduces the severity of liver disease in children with NAFLD...
  36. pmc Nonalcoholic fatty liver disease as a comorbidity of childhood obesity
    Nicole J Barshop
    Department of Pediatrics, University of California, San Diego, California, CA 92103, USA, Tel 1 619 543 7544
    Ped Health 3:271-281. 2009
    ..This review focuses on the recent advancements in the understanding of the epidemiology, diagnosis, histology, pathogenesis and treatment of pediatric NAFLD and highlights ongoing challenges and unmet needs in the area...
  37. doi request reprint The effect of cysteamine bitartrate on adiponectin multimerization in non-alcoholic fatty liver disease and healthy subjects
    Ranjan Dohil
    Department of Pediatrics, University of California, San Diego, San Diego, CA 92103 8450, USA
    J Pediatr 161:639-45.e1. 2012
    ..To determine the effects of cysteamine on adiponectin multimerization in sera of patients with nonalcoholic fatty liver disease (NAFLD)...
  38. pmc Relaxation effects in the quantification of fat using gradient echo imaging
    Mark Bydder
    MR3 Research Building, University of California San Diego, San Diego, CA 92103 8226, USA
    Magn Reson Imaging 26:347-59. 2008
    ..At short echo times, the spectral broadening effects manifest as a short apparent T2 for the fat component...
  39. pmc Cross-sectional analysis of health-related quality of life in pediatric liver transplant recipients
    Estella M Alonso
    Department of Pediatrics, Children s Memorial Hospital, 2300 Children s Plaza, Box 65, Chicago, IL 60614, USA
    J Pediatr 156:270-6.e1. 2010
    ..To investigate the distribution of health-related quality of life in pediatric liver transplant recipients compared with a normative population...
  40. pmc Quality of life in adults with nonalcoholic fatty liver disease: baseline data from the nonalcoholic steatohepatitis clinical research network
    Kristin David
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego, La Jolla, CA 92103, USA
    Hepatology 49:1904-12. 2009
    ..6), or bridging fibrosis (44.6). Cirrhosis was associated with poorer physical health after adjusting for potential confounders. Mental health scores did not differ between participants with and without NASH or by degree of fibrosis...
  41. ncbi request reprint Chronic granulomatous disease caused by a deficiency in p47(phox) mimicking Crohn's disease
    Jeannie S Huang
    Department of Pediatric Gastroenterology, Hepatology, and Nutrition, University of California, San Diego 92103 8450, USA
    Clin Gastroenterol Hepatol 2:690-5. 2004
    ..These 2 cases emphasize the importance of high clinical suspicion for an alternative diagnosis of immune deficiency in the setting of presumed inflammatory bowel disease and opportunistic infection...
  42. pmc Identification of EpCAM as the gene for congenital tufting enteropathy
    Mamata Sivagnanam
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California San Diego, La Jolla, California, USA
    Gastroenterology 135:429-37. 2008
    ..The pathogenesis and genetics of this disorder are not well understood. The objective of this study was to identify the gene responsible for CTE...
  43. ncbi request reprint Microvascular hepatic artery reconstruction in pediatric abdominal transplantation: pearls and pitfalls
    Richard Bodor
    Veterans Affairs Medical Center, San Diego Division of Plastic and Reconstructive Surgery, University of California San Diego, 200 West Arbor Drive, San Diego, CA 92103, USA
    Pediatr Transplant 11:471-6. 2007
    ..We describe our technique of hepatic artery reconstruction and offer a systematic and multi-team collaborative approach that optimizes surgical outcomes...
  44. ncbi request reprint Drugs and the liver: advances in metabolism, toxicity, and therapeutics
    Silvia Buratti
    Division of Pediatric Gastroenterology and Nutrition, University of California, San Diego and Children s Hospital and Health Center, 92103 8450, USA
    Curr Opin Pediatr 14:601-7. 2002
    ..However, differences in clinical features, natural history, and response to treatment between children and adults require evaluation of new therapeutic options in focused pediatric clinical trials...
  45. ncbi request reprint Clinical Research Network launches TONIC trial for treatment of nonalcoholic fatty liver disease in children
    Joel E Lavine
    J Pediatr Gastroenterol Nutr 42:129-30. 2006
  46. ncbi request reprint Pediatric initiatives within the Nonalcoholic Steatohepatitis-Clinical Research Network (NASH CNR)
    Joel E Lavine
    J Pediatr Gastroenterol Nutr 37:220-1. 2003
  47. doi request reprint Fast break on the fat brake: mechanism of peroxisome proliferator-activated receptor-delta regulation of lipid accumulation in hepatocytes
    Danielle B Andrews
    Hepatology 48:355-7. 2008
  48. pmc Influence of local reference populations on upper limits of normal for serum alanine aminotransferase levels
    Brent A Neuschwander-Tetri
    Arch Intern Med 168:663-6. 2008
  49. ncbi request reprint Report of the American Gastroenterological Association (AGA) Institute Obesity Task Force
    Lee M Kaplan
    Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Gastroenterology 132:2272-5. 2007
  50. pmc Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non-alcoholic fatty liver disease
    Naga Chalasani
    Indiana University School of Medicine, 1050 Wishard Boulevard, Indianapolis, IN 46202, USA
    J Hepatol 48:829-34. 2008
    ..The relationship between severity and zonal location of steatosis and the presence of steatohepatitis and various histological features that define NASH has not been formally studied...
  51. ncbi request reprint Fatty liver: imaging patterns and pitfalls
    Okka W Hamer
    Department of Diagnostic Radiology, University Hospital of Regensburg, Regensburg, Germany
    Radiographics 26:1637-53. 2006
    ..In addition, knowledge of the risk factors and the pathophysiologic, histologic, and epidemiologic features of fat accumulation may be useful for avoiding diagnostic pitfalls and planning an appropriate work-up in difficult cases...