Dissecting microscope appearances of the small intestine in childhood : a post mortem study.

The investigation to be described in this thesis, was undertaken during the past two and a half years in the Institute of Child Health at the Royal Alexandra. Hospital for Children, Camperdown, Sydney, New South Wales, The inspiration for this study came from an interest in small intestinal morphology developed while working, first as house physician to Professor C. C Booth at the Hammersmith Hospital, London in 1963 and then as research fellow in the A. W. Morrow Department of Gastroenterology at the Royal Prince Alfred Hospital, Camperdown, Sydney, New South Wales. Whilst working in that department in 1965, a technique of examination of autolysed human small intestine at post-mortem with the dissecting microscope was learnt from Dr. G. Nicholson of New Zealand who was visiting the department. Working with Miss D. Harrison the dissecting microscope was then used in a similar way to study the morphology of the small intestinal mucosa of rats, whose small intestine had been denuded of its surface epithelium by high frequency vibration. The appearances seen were similar to that observed in the autolysed human autopsy material. In 1966 on moving to the Royal Alexandra Hospital for Children, it was observed that fresh small intestinal biopsy specimens in children when examined under the dissecting microscope, were rarely characterised by finger-like villi even when histologically normal and broad leaf-like villi were most often seen in these circumstances. This finding contrasted with the frequent observation of finger-like villi, in specimens from adults which were histologically normal, that had previously been seen at the Royal Prince Alfred Hospital. These initial experiences with small intestinal biopsy in children were published as an abstract (Walker-Smith, J.A. and Harrison, D. (1966). Small Bowel Biopsy in Children. Proc. Aust. Soc. med. Res., 2, 27.) and as a paper (Walker-Smith, J.A. (1967). Dissecting Microscope Appearance of Small Bowel Mucosa in Childhood. Arch. Dis. Childh., 42, 626.). Booth et al. had suggested in 1962 that the appearance of leaf-like villi may represent a transitional stage in the genesis of an abnormal mucosa lying between finger-like villi and a convoluted mucosa. Creamer (1964) also postulated that the appearance of leaf-like villi may be the earliest abnormality to develop in small intestinal mucosa. Thus it was considered that the demonstration of leaf-like villi in children could represent an early abnormality of the mucosa, although reported as histologically normal. Such mucosa had been biopsied from children suspected of having small intestinal disease and thus although histologically normal, had not been taken from normal children. It was clearly of importance to know whether the appearance of leaf-like villi was associated with significant disease of the small intestine and as it seemed unjustifiable to biopsy the small intestine of normal children, since there is always some risk attendant on a biopsy procedure, a post-mortem study to investigate the morphology of the small intestine in infants and children dying from non-gastroenterological disease was therefore planned. This was based on Nicholson's method, as demonstrated at Royal Prince Alfred Hospital, in 1965. Whilst working as a research fellow at the Kinderklinik, Zlirich, Switzerland in 1967, the opportunity was taken to develop a modification of the methods used to examine human autolysed material described by Nicholson and also by Creamer and Leppard (1965). The small intestine from two children was studied and a simple modification of the above methods proved to be simple and reliable. This work was undertaken independently, but with the encouragement and interest of Professor A. Prader and Dr. D. H. Shmerling. On return to the Royal Alexandra Hospital for Children a study of the small intestine in children was commenced using this method