Medicine (St Vincent's) - Research Publications
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ItemAn Interesting Case of Recurrent Small Bowel Obstruction.(S. Karger AG, 2009-11-21)Sclerosing mesenteritis is associated with a spectrum of diseases which include mesenteric lipodystrophy and mesenteric panniculitis. This inflammatory and fibrosing disorder can affect the small and large bowel wall and mesenteric vessels by exerting a mass effect. The following case highlights the difficulties with diagnosing and managing this unusual disease. A 64-year-old man presented with acute central abdominal pain, radiating to his back, and profuse vomiting. He was diagnosed clinically with small bowel obstruction. He had had an episode of small bowel obstruction 6 years earlier. At this time, he underwent an exploratory laparotomy, and a mass was identified in the small bowel mesentery. The features were thought to be in keeping with sclerosing mesenteritis. He had a dramatically favourable response to the initiation of prednisolone. He continued to be well and asymptomatic for a further 5 years on long-term maintenance low-dose steroids and 6-mercaptopurine. He re-presented in 2009 (six years after initial presentation) with very severe acute abdominal pain and vomiting. He had no recent change in weight or appetite, and had not had time off work. He underwent a second laparotomy and the tissue diagnosis was of metastatic carcinoid tumour involving the small bowel mesentery. This is the first case to our knowledge where sclerosing mesenteritis has been confirmed histologically on biopsy and then subsequently diagnosed with histologically proven carcinoid tumour. For this particular reason it must be always remembered that sclerosing mesenteritis is a 'pathological' and not a radiological diagnosis and that a large proportion of cases are associated with neoplasia.
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ItemHuman 5-HT4 and 5-HT7 receptor splice vairants: Are they important?(BENTHAM SCIENCE PUBL LTD, 2007)G-protein-coupled receptors (GPCRs), which are encoded by >300 genes in the human genome, are by far the largest class of targets for modern drugs. These macromolecules display inherent adaptability of function, which is partly due to the production of different forms of the receptor protein. These are commonly called 'isoforms' or 'splice variants' denoting the molecular process of their production/assembly. Not all GPCRs are expressed as splice variants, but certain subclasses of 5-HT receptors are for example, the 5-HT(4) and 5-HT(7) receptors. There are at least 11 human 5-HT(4) and three h5-HT(7) receptor splice variants. This review describestheir discoveries, nomenclature and structures. The discovery that particular splice variants are tissue specific (or prominent) has highlighted their potential as future drug targets. In particular, this review examines the functional relevance of different 5-HT(4) and 5-HT(7) receptor splice variants. Examples are given to illustrate that splice variants have differential modulatory influences on signalling processes. Differences in agonist potency and efficacies and also differences in desensitisation rates to 5-HT occur with both 5-HT(4) and 5-HT(7) receptor splice variants. The known and candidate signalling systems that allow for splice variant specific responses include GPCR interacting proteins (GIPs) and GPCR receptor kinases (GRKs) which are examined.Finally, the relevance of 5-HT receptor splice variants to clinical medicine and to the pharmaceutical industry is discussed.
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ItemReview of tips experience at a victorian tertiary hospital(WILEY-BLACKWELL PUBLISHING, INC, 2009-10)