Journal of Pediatric Gastroenterology and NutritionVolume 66, Issue S1 p. S54-S54 Supplement Chapter 5. Fifty Years of Paediatric Gastroenterology Olivier Goulet, Corresponding Author Olivier Goulet [email protected] Divison of Pediatric Gastroenterology-Hepatology-Nutrition, Hôpital Necker-Enfants Malades, University Cité-Paris Sorbonne, Paris Descartes Medical School, Paris, FranceAddress correspondence and reprint requests to Olivier Goulet, MD, PhD, Hôpital Necker University of Paris Descartes, Paris, France (e-mail: [email protected]).Search for more papers by this authorRicardo Troncone, Ricardo Troncone Department of Translational Medical Sciences, European Laboratory for the Investigation of Food-Induced Diseases (ELFID), University of Naples Federico II, Naples, ItalySearch for more papers by this authorMarku Makki, Marku Makki Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, FinlandSearch for more papers by this authorJacques Schmitz, Jacques Schmitz Hôpital Necker-Enfants malades, University Paris-Descartes, Paris, FranceSearch for more papers by this authorIsabel Polanco, Isabel Polanco Facultad de Medicina, Universidad Autónoma de Madrid, SpainSearch for more papers by this authorMaria Luisa Mearin, Maria Luisa Mearin Department of Pediatrics, Leiden University Medical Center, Leiden, The NetherlandsSearch for more papers by this authorSamy Cadranel, Samy Cadranel Queen Fabiola Children's Hospital, Free University of Brussels, BelgiumSearch for more papers by this authorSibylle Koletzko, Sibylle Koletzko Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, GermanySearch for more papers by this authorGiuseppina Oderda, Giuseppina Oderda Università del Piemonte Orientale, Novara, ItalySearch for more papers by this authorAlan Phillips, Alan Phillips UCL Emeritus Professor of Paediatric Gastroenterology, UCL Medical School, London, UKSearch for more papers by this authorSimon Murch, Simon Murch Warwick University, London, UK University Hospital Coventry & WarwickshireSearch for more papers by this authorJohn Walker-Smith, John Walker-Smith University of London, London, UKSearch for more papers by this authorFrank Ruemmele, Frank Ruemmele Necker Enfants Malades Hospital, Pediatric Gastroenteroloy, Université Paris Descartes—Sorbonne Paris Centre, Paris, FranceSearch for more papers by this authorJorge-Amil Dias, Jorge-Amil Dias Hospital S. João, University of Porto, PortugalSearch for more papers by this authorSanja Kolacek, Sanja Kolacek University Department of Pediatrics, Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital, Zagreb, CroatiaSearch for more papers by this authorYigael Finkel, Yigael Finkel Department of Gastroenterology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorJohn Puntis, John Puntis Leeds Teaching Hospitals NHS Trust, London, UKSearch for more papers by this authorAntonella Diamanti, Antonella Diamanti Artificial Nutrition Unit, “Pediatric Hospital Bambino Gesù,”, Rome, ItalySearch for more papers by this authorSusan Hill, Susan Hill Department of Paediatric Gastroenterology, Great Ormond Street Hospital NHS Foundation Trust, London, UKSearch for more papers by this authorFlorence Lacaille, Florence Lacaille Department of Paediatric Gastroenterology-Hepatology-Nutrition, National Reference Center for Rare Digestive Disease, Reference Center for Home Parenteral Nutrition, Hôpital Necker Enfants Malades, Paris, FranceSearch for more papers by this authorGirish Gupte, Girish Gupte XXXSearch for more papers by this authorJean Francois Mougenot, Jean Francois Mougenot Hospitals Robert Debré and Necker-Enfants Malades, AP Paris, FranceSearch for more papers by this authorMike Thompson, Mike Thompson Sheffield Children's Hospital NHS Foundation Trust, Sheffield, UKSearch for more papers by this authorMarc Benninga, Marc Benninga Department of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital/Academic Medical Centre, Amsterdam, The NetherlandsSearch for more papers by this authorNikhil Thapar, Nikhil Thapar Division of Neurogastroenterology & Motility, Department of Paediatric Gastroenterology, Great Ormond Street Hospital, London, UKSearch for more papers by this authorAnnamaria Staiano, Annamaria Staiano Department of Translational Medical Science, Section of Paediatrics, University of Naples Federico II, Naples, ItalySearch for more papers by this authorGigi Veereman, Gigi Veereman Pediatric Gastroenterology and Nutrition, University Hospital Brussels, Free University Brussels, BelgiumSearch for more papers by this authorYvan Vandenplas, Yvan Vandenplas Department of Pediatrics, UZ Brussel, Vrije Universiteit Brussel, Brussels, BelgiumSearch for more papers by this authorPeter Milla, Peter Milla Division of Neurogastroenterology & Motility, Department of Paediatric Gastroenterology, Great Ormond Street Hospital, London, UKSearch for more papers by this authorJehan-François Desjeux, Jehan-François Desjeux Académie nationale de médecine, Paris, FranceSearch for more papers by this authorAlfredo Guarino, Alfredo Guarino Department of Translational Medical Science, Section of Pediatrics University of Naples Federico II, Naples, ItalySearch for more papers by this authorHania Szajewska, Hania Szajewska Department of Paediatrics, The Medical University of Warsaw, Warsaw, PolandSearch for more papers by this author Olivier Goulet, Corresponding Author Olivier Goulet [email protected] Divison of Pediatric Gastroenterology-Hepatology-Nutrition, Hôpital Necker-Enfants Malades, University Cité-Paris Sorbonne, Paris Descartes Medical School, Paris, FranceAddress correspondence and reprint requests to Olivier Goulet, MD, PhD, Hôpital Necker University of Paris Descartes, Paris, France (e-mail: [email protected]).Search for more papers by this authorRicardo Troncone, Ricardo Troncone Department of Translational Medical Sciences, European Laboratory for the Investigation of Food-Induced Diseases (ELFID), University of Naples Federico II, Naples, ItalySearch for more papers by this authorMarku Makki, Marku Makki Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, FinlandSearch for more papers by this authorJacques Schmitz, Jacques Schmitz Hôpital Necker-Enfants malades, University Paris-Descartes, Paris, FranceSearch for more papers by this authorIsabel Polanco, Isabel Polanco Facultad de Medicina, Universidad Autónoma de Madrid, SpainSearch for more papers by this authorMaria Luisa Mearin, Maria Luisa Mearin Department of Pediatrics, Leiden University Medical Center, Leiden, The NetherlandsSearch for more papers by this authorSamy Cadranel, Samy Cadranel Queen Fabiola Children's Hospital, Free University of Brussels, BelgiumSearch for more papers by this authorSibylle Koletzko, Sibylle Koletzko Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, GermanySearch for more papers by this authorGiuseppina Oderda, Giuseppina Oderda Università del Piemonte Orientale, Novara, ItalySearch for more papers by this authorAlan Phillips, Alan Phillips UCL Emeritus Professor of Paediatric Gastroenterology, UCL Medical School, London, UKSearch for more papers by this authorSimon Murch, Simon Murch Warwick University, London, UK University Hospital Coventry & WarwickshireSearch for more papers by this authorJohn Walker-Smith, John Walker-Smith University of London, London, UKSearch for more papers by this authorFrank Ruemmele, Frank Ruemmele Necker Enfants Malades Hospital, Pediatric Gastroenteroloy, Université Paris Descartes—Sorbonne Paris Centre, Paris, FranceSearch for more papers by this authorJorge-Amil Dias, Jorge-Amil Dias Hospital S. João, University of Porto, PortugalSearch for more papers by this authorSanja Kolacek, Sanja Kolacek University Department of Pediatrics, Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital, Zagreb, CroatiaSearch for more papers by this authorYigael Finkel, Yigael Finkel Department of Gastroenterology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorJohn Puntis, John Puntis Leeds Teaching Hospitals NHS Trust, London, UKSearch for more papers by this authorAntonella Diamanti, Antonella Diamanti Artificial Nutrition Unit, “Pediatric Hospital Bambino Gesù,”, Rome, ItalySearch for more papers by this authorSusan Hill, Susan Hill Department of Paediatric Gastroenterology, Great Ormond Street Hospital NHS Foundation Trust, London, UKSearch for more papers by this authorFlorence Lacaille, Florence Lacaille Department of Paediatric Gastroenterology-Hepatology-Nutrition, National Reference Center for Rare Digestive Disease, Reference Center for Home Parenteral Nutrition, Hôpital Necker Enfants Malades, Paris, FranceSearch for more papers by this authorGirish Gupte, Girish Gupte XXXSearch for more papers by this authorJean Francois Mougenot, Jean Francois Mougenot Hospitals Robert Debré and Necker-Enfants Malades, AP Paris, FranceSearch for more papers by this authorMike Thompson, Mike Thompson Sheffield Children's Hospital NHS Foundation Trust, Sheffield, UKSearch for more papers by this authorMarc Benninga, Marc Benninga Department of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital/Academic Medical Centre, Amsterdam, The NetherlandsSearch for more papers by this authorNikhil Thapar, Nikhil Thapar Division of Neurogastroenterology & Motility, Department of Paediatric Gastroenterology, Great Ormond Street Hospital, London, UKSearch for more papers by this authorAnnamaria Staiano, Annamaria Staiano Department of Translational Medical Science, Section of Paediatrics, University of Naples Federico II, Naples, ItalySearch for more papers by this authorGigi Veereman, Gigi Veereman Pediatric Gastroenterology and Nutrition, University Hospital Brussels, Free University Brussels, BelgiumSearch for more papers by this authorYvan Vandenplas, Yvan Vandenplas Department of Pediatrics, UZ Brussel, Vrije Universiteit Brussel, Brussels, BelgiumSearch for more papers by this authorPeter Milla, Peter Milla Division of Neurogastroenterology & Motility, Department of Paediatric Gastroenterology, Great Ormond Street Hospital, London, UKSearch for more papers by this authorJehan-François Desjeux, Jehan-François Desjeux Académie nationale de médecine, Paris, FranceSearch for more papers by this authorAlfredo Guarino, Alfredo Guarino Department of Translational Medical Science, Section of Pediatrics University of Naples Federico II, Naples, ItalySearch for more papers by this authorHania Szajewska, Hania Szajewska Department of Paediatrics, The Medical University of Warsaw, Warsaw, PolandSearch for more papers by this author First published: 01 April 2018 https://doi.org/10.1002/j.1536-4801.2018.tb00037.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. 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Journal of Pediatric Gastroenterology and NutritionVolume 66, Issue S1 p. S59-S64 Supplement Chapter 5.1.2. Infectious Diarrhoea Alan Phillips, Alan PhillipsSearch for more papers by this authorSimon Murch, Simon MurchSearch for more papers by this authorJohn Walker-Smith, John Walker-SmithSearch for more papers by this author Alan Phillips, Alan PhillipsSearch for more papers by this authorSimon Murch, Simon MurchSearch for more papers by this authorJohn Walker-Smith, John Walker-SmithSearch for more papers by this author First published: 01 April 2018 https://doi.org/10.1002/j.1536-4801.2018.tb00040.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. 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Journal of Pediatric Gastroenterology and NutritionVolume 66, Issue S1 p. S68-S70 Supplement Chapter 5.1.4. Paediatric Immune–related Enteropathies Frank M. Ruemmele, Frank M. RuemmeleSearch for more papers by this authorJohn Walker-Smith, John Walker-SmithSearch for more papers by this authorJorge-Amil Dias, Jorge-Amil DiasSearch for more papers by this authorOlivier Goulet, Olivier GouletSearch for more papers by this authorSimon Murch, Simon MurchSearch for more papers by this author Frank M. Ruemmele, Frank M. RuemmeleSearch for more papers by this authorJohn Walker-Smith, John Walker-SmithSearch for more papers by this authorJorge-Amil Dias, Jorge-Amil DiasSearch for more papers by this authorOlivier Goulet, Olivier GouletSearch for more papers by this authorSimon Murch, Simon MurchSearch for more papers by this author First published: 01 April 2018 https://doi.org/10.1002/j.1536-4801.2018.tb00042.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. 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Response to autoimmune enteropathy to cyclosporin A therapy. Gut 1991; 32: 1421–1425. 10.1136/gut.32.11.1421 CASPubMedWeb of Science®Google Scholar 20.Baud O, Goulet O, Canioni D, et al. Treatment of the immune dysregulation, polyendocrinopathy, enteropathy, and X-linked syndrome (IPEX) by allogeneic bone marrow transplantation. N Engl J Med 2001; 344: 1758–1762. 10.1056/NEJM200106073442304 CASPubMedWeb of Science®Google Scholar 21.Sanderson IR, Risdon RA, Walker-Smith JA. Intractable ulcerating enterocolitis of infancy. Arch Dis Child 1991; 66: 295–299. 10.1136/adc.66.3.295 CASPubMedWeb of Science®Google Scholar 22.Ruemmele FM, El Khoury MG, Talbotec C, et al. Characteristics of inflammatory bowel disease with onset during the first year of life. J Pediatr Gastroenterol Nutr 2006; 43: 603–609. 10.1097/01.mpg.0000237938.12674.e3 PubMedWeb of Science®Google Scholar 23.Thapar N, Shah N, Ramsay AD, et al. Long-term outcome of intractable ulcerating enterocolitis of infancy. 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Differences in the management of pediatric and adult onset ulcerative colitis--lessons from the joint ECCO and ESPGHAN consensus guidelines for the management of pediatric ulcerative colitis. J Crohns Colitis 2014; 8: 1–4. 10.1016/j.crohns.2013.10.006 PubMedWeb of Science®Google Scholar Volume66, IssueS1April 2018Pages S68-S70 ReferencesRelatedInformation

Early-onset inflammatory bowel disease (IBD) has a distinct phenotype and should be considered as a specific entity. IBD of very early onset includes ulcerative colitis, Crohn's disease, and a relatively high proportion of indeterminate colitis. Overall, the disease manifestations are primarily colonic, with severe perianal disease, and severe extra-gastrointestinal manifestations. Early-onset IBD presents with very severe manifestation and guarded prognosis with life-threatening signs and symptoms and needs an aggressive therapeutic approach. Early-onset IBD is unique in its association to metabolic diseases, neutrophil defects, and immunodeficiency states, chronic granulomatous disease, neutropenia, cyclic neutropenia, Wiskott-Aldrich syndrome, leukocyte adhesion defect, hypogammaglobulinemia, common variable immunodeficiency, and other immunodeficiency states. Early-onset IBD can be associated with Hermansky-Pudlak syndrome, glycogen storage disease type I B, primary defects in tryptophan handling, and familial Mediterranean fever. It is controversial whether the ensuing Intestinal inflammation in metabolic disorders, neutrophil defects and immunodeficeincy states are a form of Crohn's disease and ulcerative colitis, or a presentation of the primary disease. The very early-onset IBD presents a unique opportunity to study the impact of immunological status, neutrophil role, phagocytic function, gut microflora, metabolic pathways, and environmental factors on the genetic predisposition and the natural history of IBD. Copyright (C) 2009 S. Karger AG, Basel

Between 1966 and 2000 the pattern of gastroenterological disease in children in developed communities changed. Clinically severe infective gastroenteritis has declined in incidence. Infection of children with the conventional serotypes of Escherichia coli dramatically declined. During this period many new infective agents notably rota virus were recognised. By contrast, more children with chronic inflammatory bowel disease (IBD), especially Crohn's disease, have been diagnosed than ever before. Gastrointestinal allergy is increasingly recognised but the pattern of disease has changed. Technological advance in accurate diagnosis occurred with an emphasis upon tissue diagnosis. Introduction to clinical practice of ileocolonoscopy in the late 1970s immensely increased the ability to make the diagnosis of chronic IBD in children. Therapeutic advance has seen development of parenteral nutrition and enteral feeding as major therapies for children. In the UK there has been a rise and fall in university departments of paediatric gastroenterology.

The correspondence is reported of Sir George Newman, the first Chief Medical Officer of the United Kingdom, during his school and university education. Extracts are included of this hitherto unpublished correspondence with his family members. His conception of idealistic service to the community, first enunciated in his school days, was expanded by practical action as a medical student among the urban poor of the Cowgate, Edinburgh. The correspondence reveals his unmarried maternal aunt as the person who influenced him most.

Food allergy may affect the gastrointestinal tract of children and adults too, albeit less commonly. The changing clinicopathological expression of such food allergy in children over a 30 year period is related, from the eye witness perspective of a paediatric gastroenterologist in London. Tissue diagnosis by biopsy, related to dietary elimination and challenge has been the basis for the first clinicopathological descriptions and accurate clinical diagnosis of these syndromes as they affect the gastrointestinal tract. In the 1970s cow's milk sensitive enteropathy presenting as chronic diarrhoea and failure to thrive in infancy often after infective gastroenteritis, especially with enteropathogenic Escherichia coli, was an important problem. By the late 1990s such presentations had become most uncommon in developed communities but they continue to occur in developing communities. By contrast in more recent times, multiple food allergy associated with minor small intestinal enteropathy and gastro-oesophageal reflux in older children has become an important clinical problem in children seen in developed communities. Accompanying these changes has been a dramatic fall in the number of children with clinically severe gastroenteritis with severe dehydration requiring hospital admission. Furthermore, the widespread diagnostic use of endoscopy of the upper and lower gastrointestinal tract in children with multiple biopsies has expanded gastroenterological diagnosis in children. This approach gives information about the oesophagus and ileo-colon not available in the earlier studies, which largely concentrated upon small intestinal biopsies, obtained by Crosby capsule biopsy. So, over this 30 year period clinico-pathological expression has altered but also the diagnostic approach has technically changed.

I deny the allegation that there was systematic bias in the pattern of referral for the children in the 1998 Lancet paper. No children were invited to participate in the study. Upon review of the Centre for Paediatric Gastroenterology, Royal Free Hospital, work book entitled “Biopsies VI 4/9/95 to 21/7/97”, we confirm that the children who were reported in the Lancet paper of 1998 were the first 12 children consecutively referred to the university department of paediatric gastroenterology with autism and related disorders, who had gastrointestinal symptoms requiring ileo-colonoscopy to exclude chronic bowel inflammation. These children were referred to me at the university department of paediatric gastroenterology at the Royal Free Hospital from July 25, 1996, to February 24, 1997—one being referred from the island of Jersey and one from the USA. By the time the paper was accepted for publication, as mentioned in an appendix to the Lancet paper, up to January 28, 1998, a further 40 children had been so investigated, 39 with the syndrome reported in the paper. The children were all investigated specifically and exclusively by clinical need to determine whether bowel inflammation was present that could then be appropriately treated. These children were referred to the Royal Free by their general practitioner (ten cases) or consultant paediatrician (two cases). Some parents had heard of Dr Wakefield's previous work on inflammatory bowel disease and specifically requested referral, but the channel of referral was always as described above. However, the pattern of referral was often that the parents of the children approached Dr Wakefield directly knowing of his work, frequently by telephone. In the case of one patient, in whom it has been alleged that I contacted a consultant in order for a referral to be made, he had been asked by the parents of this child to contact me to explain what investigations were available at the Royal Free for children with autism and bowel problems. To the best of my recollection, I did not invite any children to participate in our study. None of the children at the time of the referral was known by the team of paediatric gastroenterologists who cared for and investigated these children to be involved in a pilot project commissioned by the Legal Aid Board. At the time of consultation, I was aware that some parents were engaged in legal proceedings. Review of the clinical notes of the 12 children in the 1998 Lancet paper indicate that we had become aware at the time of publication that one child was involved in litigation proceedings against the vaccine manufacturers.

In the fifth article in this series, Drs. Walker-Smith and Walker describe the evolution of the specialty of pediatric gastroenterology. They make the point that the specialty evolved because of the perception of the special needs of children with gastrointestinal disease. They present not only the history of the advances in this field but also the many contributions of the clinicians and scientists whose work led to the establishment of this specialty. These experts developed societies, journals, and training programs providing, thereby, optimum care and study of children with gastrointestinal disease.

Charlotte Anderson died on April 15, 2002, at the age of 87 years. She died in Melbourne, where she was born on March 12, 1915. She was a founding member of the European Society of Pediatric Gastroenterology (now ESPGHAN) at its first meeting in Paris in 1968. She was a member of the first council of ESPGHAN and organized the 1970 annual meeting of the society in Birmingham. She has been described by some as the grandmother of pediatric gastroenterology. It is clear that she was one of the pioneers of the discipline, first of all in the land of her birth, Australia, then in Britain, but also in the European society and beyond in the wider world. The first edition of her book, “Paediatric Gastroenterology” (with Valerie Burke as co-author), was published in 1974. As one of the first such books in the English language, it was an immediate success. It was influential in the dissemination of knowledge of the discipline. Charlotte Anderson made a notable contribution to the development of pediatrics itself. She had the distinction to be appointed as the first woman professor of Pediatrics in the United Kingdom in 1968. She also made important contributions to the development of clinical research within pediatrics as a whole, in addition to pediatric gastroenterology. Her commitment to research related to the fact that she had graduated first in science as a Bachelor of Science from the University of Melbourne with honors in 1935, followed by a Masters of Science. She then went on to graduate in medicine in 1945. She became a Doctor of Medicine of the University of Melbourne in 1955 with her thesis entitled “Diagnosis, Aetiology and Treatment of Coeliac Disease”, based upon the work she undertook in celiac disease in Birmingham. In this obituary, first her contribution to the expansion of knowledge concerning gastroenterological problems in children, including cystic fibrosis, will be discussed and second her contribution to the development of the discipline. It is no accident that she was a science graduate, as she always saw the necessity for research as a basis for clinical knowledge of the disease processes in children. She was most proud of her work concerning the malabsorption syndromes. She was particularly proud of her simple ward test for the presence of excess-reducing substances in the stools of infants, described with K. R. Kerry in the Lancet in 1964 and now an internationally used simple diagnostic test for infants with chronic watery diarrhea. There were several important papers with Valerie Burke as first author, describing the clinical syndromes of secondary sugar intolerance as a cause of chronic infantile diarrhea. She also made notable contributions to the knowledge of both celiac disease and cystic fibrosis. Her work on celiac disease was particularly important. Traveling as a ship's doctor, she came to England in 1950 as a research fellow with Sir Wilfrid Sheldon at Great Ormond St., well known for his interest in celiac disease. He subsequently sent her to Birmingham as a research fellow to join the remarkable team of Professor Alistair Frazer and Dr. Jack French who were then studying fat absorption in celiac disease. She gave an account of this period in 1988 when she attended the International Symposium on Celiac Disease: One Hundred Years at St. Bartholomew's Hospital. She presented a paper describing Birmingham's contribution to celiac disease in the early 1950s. This research followed upon the demonstration of the harmful effects of wheat and rye flour on the absorption of fat in children with celiac disease made by Dicke, Weijers, and Van de Kamer in Utrecht. Long-term fat excretion studies in Birmingham demonstrated that the harmful agent was the gluten part of flour. These observations were published in the Lancet in 1952, in fact before the Dutch workers' publication, because of, as Dr. Anderson stated it, “their difficulty in having the paper accepted and published by a journal with an international readership until 1953”. It was this paper that led to her return to Melbourne in 1953 where she continued her research on celiac disease. She also set up Australia's first cystic fibrosis clinic. She developed a technically reliable method of sweat collection in 1958 to enable an accurate diagnosis of cystic fibrosis to be made. She also introduced the technique of small intestinal biopsy to Royal Children's Hospital Melbourne in 1958 following a study tour of Europe and America. Of immense importance was her paper in 1960 from Melbourne that contained the key observation that the abnormal small intestinal mucosa in children with celiac disease normalized on a gluten-free diet. In 1961, she and her colleagues described chylomicron retention disease as an unusual cause of steatorrhea. This has since sometimes been called Anderson's Disease. She formed a Gastroenterological Unit within the Royal Children's Hospital Research Foundation and was appointed its head in 1962. In 1968 she accepted the Leonard Parsons Chair in Paediatrics and Child Health at the University of Birmingham. Her view was that specialization was essential if pediatrics was to prosper; hence her commitment to the advancement of pediatric gastroenterology. Her interest in cystic fibrosis continued. With Mary Goodchild, in 1976 she wrote an important manual on the diagnosis and management of cystic fibrosis. She also undertook important genetic studies of celiac disease. She made Birmingham a center for pediatric gastroenterology and played an important role in having the discipline recognized nationally and internationally. She retired in 1980 and was made an Emeritus Professor. She returned to Perth, Australia to write the second edition of “Paediatric Gastroenterology” with her long-term colleagues and friends Valerie Burke and Michael Gracey. Some years later she came back to her roots in Melbourne but continued from time to time to travel back to Britain and Europe. Amongst her many contributions to pediatric gastroenterology were the young people she trained, inspired, and encouraged to take up a career in the emerging discipline. It is not possible to give a full list, but notably these individuals include Valerie Burke and her husband Michael Gracey, Beat Hadorn, Sandy McNeish, and Martin Brueton. At a wider level she was an inspiration to many internationally, including many women such as Birgitte Strandvik who saw her as a role model. Interestingly Charlo's (as she was affectionately called by her friends) last attendance at an ESPGHAN meeting was in Gothenburg at the meeting hosted by Birgitte Strandvik in 1993. It is well known that her child patients and their parents, especially those with cystic fibrosis, were devoted to her, both in Australia and Britain. Lasting memories of her in Birmingham include her forceful personality and the presence in her office of a succession of pet poodles. Those of us in ESPGHAN who knew her mourn her passing as one of the pioneers of pediatric gastroenterology and regard it as a privilege to have known her. FIGUREFigure

Journal of Pediatric Gastroenterology and NutritionVolume 34, Issue S1 p. S68-S76 Article Recollections and Reflections on the Medical Life, Student and Doctor, 1954 to 2000 John Walker-Smith, John Walker-Smith University Department of Paediatric Gastroenterology, Royal Free Campus, Royal Free and University College Medical School, University College, London, United KingdomSearch for more papers by this author John Walker-Smith, John Walker-Smith University Department of Paediatric Gastroenterology, Royal Free Campus, Royal Free and University College Medical School, University College, London, United KingdomSearch for more papers by this author First published: 01 May 2002 https://doi.org/10.1002/j.1536-4801.2002.tb07712.xCitations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat REFERENCES 1Turney C, Bygott U, Chippendale P. Australia's First. A History of the University of Sydney. Vol. 1. 1850-1939. Sydney: Hale and Iremonger, University of Sydney; 1991. Google Scholar 2Epps W. Anderson Stuart MD. Sydney: Angus and Robertson; 1922. Google Scholar 3Warden A, Watson B. Sydney Church of England Grammar School, Register 1889-1994. Sydney: Bridge Printery; 1994. Google Scholar 4Gorham JR, Hewett CJL. The Torch Bearers. War Service of Shore Old Boys 1939-1999. Sydney: Shore Sydney Church of England Grammar School; 1999. Google Scholar 5 Obituary. Angus Buchanan Walker-Smith. BMJ 1975. Google Scholar 6Young JA, Sefton AJ, Webb N. Centenary Book of the University of Sydney Faculty of Medicine. Sydney: Sydney University Press; 1984: 158–60. Google Scholar 7Tzedakisy, Martlew H. Minoars and Mycenaens flavours of their time. Exhibit at the National Archeological Museum Athens; 1999. Google Scholar 8Sefton AJ, Cheng N, Thong IA. The Centenary Book of the Sydney University Medical Society. Sydney: Hale and Iremonger; 1992: 151. Google Scholar 9Court D. Paediatrics in the seventies. BPA 1970. Google Scholar 10Kosky J. Queen Elizabeth Hospital for Children, 125 years of Achievement. The Hospitals for Sick Children; 1992. Google Scholar 11Walker-Smith JA. Tomlinson Report. BMJ 1992; 305: 1289. 10.1136/bmj.305.6864.1289-c CASPubMedGoogle Scholar 12Wilmore DW, Dudrick SJ. Growth and development of an infant receiving all nutrients exclusively via vein. JAMA 1968; 20: 860–4. 10.1001/jama.1968.03140100042009 Google Scholar 13Walker-Smith JA. Autism, inflammatory bowel disease and MMR vaccine. Lancet 1998; 351: 1356–7. 10.1016/S0140-6736(05)79084-X CASPubMedGoogle Scholar Citing Literature Volume34, IssueS1May 2002Pages S68-S76 ReferencesRelatedInformation

When diarrhoea caused by gastroenteritis persists for more than two weeks it is referred to as persistent diarrhoea in developing countries. Whilst the Control of Diarrhoeal Diseases programme has decreased mortality from acute diarrhoea, mortality from persistent diarrhoea has not been so responsive. A number of factors have been identified which are determinants for the progression of an acute episode to one which persists in developing communities. In one study from west Africa, current infection with Cryptosporidium parvum was the most significant factor. In studies from Brazil and India, continuing infection with enteropathogenic Escherichia coli was identified in 50% of infants with persistent diarrhoea. Persistent small intestinal mucosal damage is of key importance in such children. Management of established cases is complex and difficult. However, there is clear evidence that zinc is involved in the recovery of small intestinal mucosa after injury. Zinc supplementation may indeed significantly reduce the duration of persistent diarrhoea. However, the whole question of public health supplementation with zinc, vitamin A, or other supplements, is contentious at present.

In this issue, volume 28 (1), January 1999, we begin our fourth and fifth years, respectively, as editors of the Journal. By an overwhelming majority the combined Editorial Boards of ESPGHAN and NASPGN at the joint meeting in Toulouse approved a "new" section for the Journal entitled, "News and Views." This section is intended to inform the worldwide readership in a timely manner about clinical, research, and political issues that may interest the pediatric gastroenterologist and/or care providers of children with gastrointestinal disease. The Journal welcomes letters to the editor in response to the chosen topics. Drs. Philip Sherman (NASPGN) and Hams Büller (ESPGHAN) will be the section Editors. Please correspond with them or with Drs. Walker-Smith or Walker about topics to be considered. The time for publication of this section will be streamlined in order to publish items in a timely manner. With the first issue, we will address: (1) "The Need for Evidence-based Care in the Daily Practice of Pediatric Gastroenterology," (2) "Recertification or Maintenance of Certification By Decree or by Choice?" and (3) "The Hunt for Inflammatory Bowel Disease Susceptibility Genes: Where Are Linkage Studies Taking Us?" On another note, I, Allan Walker, wish to thank the NASPGN membership who responded to the questionnaire enclosed in the society newsletter last summer. Almost one-third of the readership responded. Your comments and ideas/suggestions are invaluable to the mission of JPGN. Your willingness to review manuscripts is also appreciated. Thank you. We are enjoying the role of Editors and hope to continue to implement a "dynamic journal" for your reading pleasure. W. Allan Walker, M.D. John Walker-Smith, M.D. Editors

90 Aims: The basement membrane (BM) of the small intestine is now recognised to regulate epithelial proliferation and maturation, as well as regulate solute and macromolecular flux. However little is known about BM alterations in small intestinal enteropathy. Methods: We have characterised both protein and carbohydrate BM components in defined enteropathies (coeliac disease [n=6], cow's milk sensitive enteropathy - CMSE [9], autoimmune enteropathy [7], epithelial dysplasia [4]) as well as in 12 normal and 5 inflammatory controls. Immunohistochemical staining for laminin, collagen IV and tenascin and cationic probe staining for glycosaminoglycans (GAGs) was performed, with quantitation of BM thickness and staining intensity along the crypt-villus axis. Results: Thickened deposition of both collagen IV and laminin, limited to the villus tip, was seen in inflammatory controls and the autoimmune and CMSE groups (7.5-10 vs 5.5-6.5 μm). BM thickness also tended to be increased within the crypts (5-6.5 vs 3-4.5 μm). Staining intensity was however increased only for laminin in the crypts and tenascin in the subepithelial basement membrane. By contrast markedly decreased staining was observed for GAGs throughout the basement membrane, notably in inflammatory controls and autoimmune enteropathy. Conclusions: We provide evidence for differential regulation of basement membrane composition in childhood enteropathies. The overall tendency is for enhanced expression of protein components in small intestinal inflammation, with concomitant loss of the carbohydrate component. This implies a restricted expression of matrix-degrading metalloproteases in inflammatory enteropathies.

110 Background: Tissue damage in IBD occurs by inflammatory degradation of extracellular matrix, notably glycosaminoglycans (GAGs -Lancet 1993; 341: 711-714). We now report the therapeutic effects of matrix restoration with N-acetyl glucosamine (NAG), a“neutraceutical” substrate for GAG production. In addition to its role as a fuel for fibroblast repair, there is recent evidence that NAG may act intracellularly as an antagonist of O-phosphorylation and may thus regulate inflammatory pathways (Annu Rev Biochem 1997; 66: 313-335). We have thus stained biopsies for GAGs and used the lectin wheatgerm agglutinin (WGA) to detect intracellular NAG. Results: Rectal administration of NAG (1.5-2 g bd) to 9 children with therapy-resistant distal colitis induced clinical remission in 4, improvement in 3 and no effect in 2. Biopsies before and after treatment showed shown histological improvement in all tested, with a striking increase in GAG density and intraepithelial WGA staining. Oral NAG therapy, in combination with existing therapies, was also commenced in 11 children with severe small intestinal and colonic disease, including 7 with critical strictures. 8/11 have shown improvement, while 3 have required surgical resection. 6/7 with treatment-resistant strictures showed marked resolution of symptoms, with endoscopic or radiological improvement in 4/6. GAG density and WGA staining was enhanced in all, to an extent greater than in other children treated with steroids or enteral nutrition. Discussion: This first uncontrolled trial suggests that NAG is potentially of therapeutic efficacy in resistant IBD. Its mode of action is distinct from conventional therapies, and its lack of known adverse effects makes it particularly suitable for paediatric use.

Pathological processes and diseases of the upper gastrointestinal tract have become increasingly recognized over recent years as childhood entities responsible for a variety of upper gastrointestinal symptoms previously labelled as functional or non-organic. The term ‘dyspepsia’ is an adult one whose definition requires clarification before use in the paediatric context, but it encompasses age-dependent symptoms such as feedassociated irritability in the infant, peri-umbilical pain in the younger child, and heartburn, nausea, and indigestion in the older child as in adults. The possible organic conditions giving rise to such symptoms are multiple and multiorgan and include: gastro-oesophageal reflux; peptic ulcer disease; upper gastrointestinal Crohn's disease; antroduodenal motility disorders; pancreatitis; cholecystitis; cholelithiasis; biliary dyskinesia; and abdominal migraine. However, Munchausen syndrome by proxy must not be forgotten. Non-ulcer dyspepsia, it is now clear, has a basis in altered gastroduodenal motility and may be amenable to propulsion agents. In many individuals the dyspeptic symptoms of recurrent abdominal pain may be altered by psychotherapeutic intervention. Indeed there remains a proportion of children who undoubtedly have a behavioural or psychological base to their complaint. Nevertheless, with the recent increase in diagnostic yield from improved technical investigative aids available to paediatrics in the last 5–10 years, it is clear that the responsibility of the paediatrician to the child to find a cause of their symptoms is paramount. The variety of presenting features, possible causes of these symptoms, and appropriate investigation and treatment will be discussed, and management algorithms based on published literature and personal practice will be offered.