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PubMed2003

7th Yahya Cohen Lecture. Significance of the lateral epiphysis of the acetabulum to hip joint stability.

Normal development of the acetabulum is crucial to the growth and stability of the hip. Twenty-five New Zealand white rabbits (postweaning) weighing 1.5 to 2.2 kg were used. Both hips were exposed through an anterolateral approach. On the right hip, a fixed area of superolateral physeal cartilage was damaged with drills. Sham open reduction was performed for the left hip. Radiographic changes of the right hips were evident at 6 weeks. At 12 weeks, the right hip dislocated in a posterior and superior direction. The left hip remained normal. Histopathologic analysis correlated strongly with the radiographic findings. There were thinning of cartilage cells of the acetabulum, with disorganisation. The acetabular roof was poorly formed. The lateral acetabular epiphysis is vital to the development of the acetabular roof. Damage to this epiphysis may result in acetabular maldevelopment and subsequent hip instability. We tested the hypothesis that abnormality in this epiphysis can give rise to abnormal acetabular development.

Acetabulum↗
PubMed2003

Runme Shaw Memorial Lecture 2002. Modern management of colorectal polyps: Are they all premalignant?

There are various types of polyps in the colon and rectum. Most colorectal polyps in the colon and rectum are either adenomas or hyperplastic polyps. In general, adenomas are considered to be premalignant. Adenoma-carcinoma sequence is an established theory of carcinogenesis in the large bowel in Western countries. However, small adenomas are ubiquitous phenomena, and it is questionable whether they are actually precancerous. Most small adenomas did not become larger in our colonoscopic follow-up study of small adenomas measuring 5 mm or less. It was considered safe to leave such small adenomas behind, particularly in a situation in which follow-up examination is periodically performed, such as in patients who have undergone colorectal cancer surgery before. In Japan, small flat carcinomas have been reported as an important precursor of advanced colorectal carcinoma. They are also found in Western population. The malignancy rate of small flat and depressed lesions was significantly higher than that of polypoid lesions. Although small flat carcinomas are less frequently seen than polypoid-type carcinomas in the early stages, they are considered to be an important precursor of advanced colorectal cancer.

Adenoma↗
PubMed2003

The Gordon Wilson Lecture. Lessons about the control of glucose homeostasis and the pathogenesis of diabetes from knockout mice.

The painstaking process of generating constitutive and conditional knockout mice has paid off handsomely. The roles of the insulin receptor and its intracellular substrates in insulin action has been established and begun to shed light onto some of the proteins less obvious functions. We have learned how genetic predisposition plays itself out in the oligogenic and heterogeneous pathogenesis of type 2 diabetes and how the balance of proteins can affect the efficiency of signaling both positively and negatively. The IRS knockout mice have taught us how these proteins provide unique and complementary signals in insulin action. From the tissue specific knockouts we have learned that [figure: see text] different tissues contribute uniquely to the pathogenesis of type 2 diabetes, but not always in the predicted way; that insulin resistance at different levels in the same tissue may produce different phenotypes; that tissues possess mechanisms of communication such that resistance in one tissue affects insulin signaling or metabolism in others; and that insulin has important effects in tissues not previously considered insulin responsive, including the brain and beta-cells. The result of this work has led us to develop new hypotheses about the nature of the insulin action network.

Adipose Tissue↗
PubMed2003

The Jeremiah Metzger Lecture. Pathogenesis of atherosclerosis: redox as a unifying mechanism.

Excessive production of reactive oxygen species (ROS) occurs in many diseases and oxidation may be a common disease mechanism generally. The original "oxidation hypothesis" concerning the pathogenesis of atherosclerosis was posited in the context of the putative central role of oxidized LDL in the process. Atherosclerosis has three major characteristic features: inflammation with accumulation of T-cells and, in particular, monocytes, which become lipid rich foam cells; remodeling of the arterial wall; and the non-random localization of lesions to areas of disturbed flow or of low shear stress. The evidence is reviewed that each of these characteristics can be attributed to excessive ROS, which are derived from cellular oxidases, especially, the NAD(P)H oxidases. This expanded concept of the central role of oxidation in the pathogenesis of atherosclerosis has led to a renewed and intense interest in the potential role of antioxidants in therapy. The vascular protective effects of existing drugs such as statins and ACE inhibitors that are not related to serum lipid alterations are attributed to their indirect but effective roles as antioxidants. These data as well as evidence that newly developed antioxidant drugs show promise, not only in experimental animals but also clinically, are reviewed.

Animals↗
PubMedDate not supplied

Forthergillian Lecture. Imaging human brain function.

The non-invasive brain scanning techniques introduced a quarter of a century ago have become crucial for diagnosis in clinical neurology. They have also been used to investigate brain function and have provided information about normal activity and pathogenesis. They have been used to investigate functional specialization in the brain and how specialized areas communicate to generate complex integrated functions such as speech, memory, the emotions and so on. The phenomenon of brain plasticity is poorly understood and yet clinical neurologists are aware, from everyday observations, that spontaneous recovery from brain lesions is common. An improved understanding of the mechanisms of recovery may generate new therapeutic strategies and indicate ways of modulating mechanisms that promote plastic compensation for loss of function. The main methods used to investigate these issues are positron emission tomography and magnetic resonance imaging (M.R.I.). M.R.I. is also used to map brain structure. The techniques of functional brain mapping and computational morphometrics depend on high performance scanners and a validated set of analytic statistical procedures that generate reproducible data and meaningful inferences from brain scanning data. The motor system presents a good paradigm to illustrate advances made by scanning towards an understanding of plasticity at the level of brain areas. The normal motor system is organized in a nested hierarchy. Recovery from paralysis caused by internal capsule strokes involves functional reorganization manifesting itself as changed patterns of activity in the component brain areas of the normal motor system. The pattern of plastic modification depends in part on patterns of residual or disturbed connectivity after brain injury. Therapeutic manipulations in patients with Parkinson's disease using deep brain stimulation, dopaminergic agents or fetal mesencephalic transplantation provide a means to examine mechanisms underpinning plastic change. Other models of plastic change, such as normal visuospatial learning or re-establishing speech comprehension after cochlear implantation in the deaf illustrate how patterns of brain function adapt over time. Limitations of the scanning techniques and prospects for the future are discussed in relation to new developments in the neuroimaging field.

Brain↗
PubMed2001

J.H. Louw Memorial Lecture. Liver surgery: 'traveller, there is no path, a path is made by walking'.

Liver resection today is a product of rapid development over the past two decades. The description of the functional anatomy of the liver was the foundation of modern liver surgery. However, it has been the technological advances in radiology that have had the biggest impact in the management of hepatobiliary disease. Major hepatectomies dominated the earlier experience of modern liver surgery, but segment-orientated resections now play a more prominent role. Resections may be performed for both malignant and benign lesions or as an emergency procedure for trauma or other catastrophic event. At Princess Alexandra Hospital, Brisbane, 1,108 liver resections have been undertaken. Of the elective resections, 45% were for metastases, 29% for primary malignancy and 26% for benign disease. Two-thirds of the 102 emergency hepatectomies were for severe liver trauma. The 30-day mortality was 3.2% for the total series, 2.6% for the elective cases and 1.5% for the elective, non-jaundiced patients. Innovative graft reduction techniques have become a major component in liver transplantation. The successful transplantation of a reduced-size segmental graft from an adult donor liver to an infant paved the way for other procedures such as split-liver, auxiliary partial orthotopic and living-donor transplantation.

Carcinoma, Hepatocellular↗