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A number of localizations for the putative susceptibility gene(s) have been identified for both Crohn's disease and ulcerative colitis. In a genome wide scan, Hugot et al. (1996) identified a region on chromosome 16 which appeared to be responsible for the inheritance of inflammatory bowel disease in a small proportion of families. Subsequent work has suggested that this localization is important for susceptibility to Crohn's disease rather than ulcerative colitis (Ohmen et al. 1996; Parkes et al. 1996). We investigated the contribution of this localization to the inheritance of inflammatory bowel disease in 54 multiplex Australian families, and confirmed its importance in a significant proportion of Crohn's disease families; we further refined the localization to a region near to D16S409, obtaining a maximum LOD score of 6.3 between D16S409 and D16S753.

The aim of this study was to compare alterations of the basement membrane zone (BMZ) and to visualize changes within the skin vascular network in morphea and extragenital lichen sclerosus with the use of laser scanning confocal microscopy. This work was performed in eight plaques of morphea (three active and five inactive) and eight of lichen sclerosus (three of short duration and five long-lasting). Biopsy specimens from six healthy individuals served as controls. The biopsies were cut into 40-microm-thick sections, labeled with antibodies against beta4-intergin (a lamina lucida marker), collagen IV, and the N-terminal end of collagen VII (lamina densa markers) and C-terminal end of collagen VII (a sublamina densa marker) and studied using laser scanning confocal microscopy. Three-dimensional reconstruction of various regions of the BMZ showed a decreased number and size of the dermal papillae both in morphea and lichen sclerosus compared with normal skin. In morphea, the continuity of the BMZ at the level of lamina lucida, lamina densa, and sublamina densa was preserved whereas in LS numerous invaginations and holes were present in the BMZ at the level of the lamina lucida and lamina densa. Thus the alterations of the BMZ in morphea differ from those in lichen sclerosus. Three-dimensional reconstruction of the skin vascular network showed increased angiogenesis only in the early inflammatory stage of morphea, whereas in inactive morphea and lichen sclerosus various numbers of enlarged vessels were visible. The changes in the vascular network in morphea appear to be related to the activity of the disease.

We have detected a number of changes in clinical and pathological aspects of colorectal cancer over a 20 year period in the ACT, including a proximal shift in the subsite distribution of colorectal cancer. These changes suggest that proximal and distal colorectal cancers may have a different aetio-pathogenesis, and have implications for the investigation of patients with suspected colorectal cancer and in screening high-risk groups.

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