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Slipped and lost muscles and other tales of the unexpected. Philip Knapp Lecture.

Loss of a rectus muscle may occur as a rare complication of strabismus surgery. In addition, extraocular muscles may become traumatically detached from the globe when they rupture or are transected as the result of an injury or during the course of retinal detachment or paranasal sinus or orbital surgery. Although the clinical features of a slipped muscle may resemble those of a lost muscle, the findings at the time of reoperation are distinct. Also the etiology, and therefore the prevention, of a slipped muscle differs from that of a lost muscle. It is likely that slipped muscles and even some lost muscles are underdiagnosed and represent a significant cause of unexpected overcorrection or undercorrection. Unless the displaced muscle is appropriately advanced, it can be extremely difficult to correct the associated strabismus, yet locating and repairing either a lost or slipped muscle can be challenging and is by no means always successful. Current concepts pertaining to the etiology, recognition, and management of slipped and lost muscles will be discussed.

Adolescent↗

Founders' Lecture.

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California↗

1997 Sir William Refshauge Lecture. Skeletal muscle glucose metabolism during exercise: implications for health and performance.

Skeletal muscle glucose uptake and metabolism are major determinants of whole body glucose metabolism in response to exercise and insulin stimulation. An understanding of the mechanisms responsible for increased muscle glucose uptake under these conditions is crucial for identifying strategies that enhance insulin action and exercise performance. Regular exercise, by favourably influencing the intramuscular determinants of glucose uptake, enhances insulin action. For this reason, it is recommended in the prevention and management of disease states that are characterised by insulin resistance ("metabolic syndrome"). Increased skeletal muscle glucose uptake, as a consequence of carbohydrate ingestion, maintains carbohydrate supply to contracting muscle, at a time when glycogen levels are reduced, and is associated with enhanced performance. Thus, both health and exercise performance are influenced by the metabolism of glucose within skeletal muscle.

Dietary Carbohydrates↗

Toynbee Memorial Lecture 1997. Middle ear mechanics in normal, diseased and reconstructed ears.

A review of the structure-function relationships in normal, diseased and reconstructed middle ears is presented. Variables used to describe the system are sound pressure, volume velocity and acoustic impedance. We discuss the following: (1) Sound can be transmitted from the ear canal to the cochlea via two mechanisms: the tympanoossicular system (ossicular coupling) and direct acoustic stimulation of the oval and round windows (acoustic coupling). In the normal ear, middle-ear pressure gain, which is the result of ossicular coupling, is frequency-dependent and smaller than generally believed. Acoustic coupling is negligibly small in normal ears, but can play a significant role in some diseased and reconstructed ears. (2) The severity of conductive hearing loss due to middle-ear disease or after tympanoplasty surgery can be predicted by the degree to which ossicular coupling, acoustic coupling, and stapes-cochlear input impedance are compromised. Such analyses are used to explain the air-bone gaps associated with lesions such as ossicular interruption, ossicular fixation and tympanic membrane perforation. (3) With type IV and V tympanoplasty, hearing is determined solely by acoustic coupling. A quantitative analysis of structure-function relationships can both explain the wide range of observed post-operative hearing results and suggest surgical guidelines in order to optimize the post-operative results. (4) In tympanoplasty types I, II and III, the hearing result depends on the efficacy of the reconstructed tympanic membrane, the efficacy of the reconstructed ossicular chain and adequacy of middle-ear aeration. Currently, our knowledge of the mechanics of these three factors is incomplete. The mechanics of mastoidectomy and stapedectomy are also discussed.

Biomechanical Phenomena↗

Sir David Cuthbertson Medal Lecture. Regulation of lipid metabolism in adipose tissue.

Adipose tissue is a major source of metabolic fuel. This metabolic fuel is stored in the form of triacylglycerol. Lipolysis of triacylglycerol yields non-esterified fatty acids and glycerol. In human subjects in vivo studies of the regulation of lipid metabolism in adipose tissue have been difficult because of the heterogeneous nature of the tissue and lack of a vascular pedicle. In the last decade the methodology of study of adipose tissue has improved with the advent of the anterior abdominal wall adipose tissue preparation technique and microdialysis. These techniques have demonstrated that lipid metabolism in adipose tissue is finely coordinated during feeding and fasting cycles, in order to provide metabolic fuel when required. Lipolysis takes place both in extracellular and intracellular space. The extracellular lipolysis is regulated by lipoprotein lipase and the intracellular lipolysis is regulated by hormone-sensitive lipase. In pathophysiological conditions such as trauma, sepsis and starvation profound changes are induced in the regulation of lipid metabolism. The increased mobilization of lipid fuel is brought about by the differential actions of various counter-regulatory hormones on adipose tissue blood flow and adipose tissue lipolysis through lipoprotein lipase and hormone-sensitive lipase, resulting in increased availability of non-esterified fatty acids as a source of fuel. In recent years, it has been demonstrated that adipose tissue produces various cytokines and these cytokines can have paracrine and endocrine effects. It would appear that adipose tissue has the ability to regulate lipid metabolism locally as well as at distant sites such as liver, muscle and brain. In future, it is likely that the mechanisms that lead to the secondary effects of lipid metabolism on atheroma, immunity and carcinogenesis will be demonstrated.

Adipose Tissue↗

The Sir David Cuthbertson Medal Lecture. Hunting for new pieces to the complex puzzle of obesity.

Disentangling the neuroendocrine systems that regulate energy homeostasis and adiposity has been a long-standing challenge in pathophysiology, with obesity being an increasingly important public health problem. Adipose tissue is no longer considered a passive bystander in body-weight regulation. It actively secretes a large number of hormones, growth factors, enzymes, cytokines, complement factors and matrix proteins, at the same time as expressing receptors for most of these elements, which influence fuel storage, mobilisation and utilisation at both central and peripheral sites. Thus, an extensive cross talk at a local and systemic level in response to specific external stimuli or metabolic changes underpins the multifunctional characteristics of adipose tissue. In addition to the already-known adipokines, such as IL, TNFalpha, leptin, resistin and adiponectin, more recently attention has been devoted to 'newcomers' to the 'adipose tissue arena', which include aquaporin, caveolin, visfatin, serum amyloid A and vascular endothelial growth factor. While in vitro and in vivo experiments have provided extremely valuable information, the advances in genomics, proteomics and metabolomics are offering a level of information not previously attainable to help unlock the molecular basis of obesity. The potential and power of combining pathophysiological observations with the wealth of information provided by the human genome, knock-out models, transgenesis, DNA microarrays, RNA silencing and other emerging technologies offer a new and unprecedented view of a complex disease, conferring novel insights into old questions by identifying new pieces to the unfinished jigsaw puzzle of obesity.

Adipocytes↗

Sir David Cuthbertson Medal Lecture. The impact of dietary protein restriction on insulin secretion and action.

The goal of this review is to develop the hypothesis, and review the evidence, that protein restriction, through synergistic effects on multiple organ systems predisposes to loss of normal regulation of fuel homeostasis that plays the central role in the development of type 2 (non-insulin-dependent) diabetes mellitus. The ability of insulin to regulate glucose production and disposal varies between individuals. These differences, together with the various compensatory mechanisms that are invoked to attempt to normalize fuel homeostasis, are of fundamental importance in the development and clinical course of type 2 diabetes mellitus. Protein deprivation impacts on both insulin secretion and insulin action. These effects may persist even when a diet containing adequate protein is presented subsequently. Data are presented that suggest that protein restriction results in an impaired ability of pancreatic beta-cells to compensate adequately for the defect in insulin action in insulin-resistant individuals. This persistent impairment of insulin secretion resulting from protein restriction predisposes to loss of glucoregulatory control and impaired insulin action after the subsequent imposition of a diabetogenic challenge. This inability to maintain the degree of compensatory hyperinsulinaemia necessary to prevent loss of glucose tolerance may have relevance to the increased incidence of diabetes on changing from a nutritionally-poor diet to a Western diet, and to the hypothesis that some cases of type 2 diabetes in adulthood may be related to poor early nutrition.

Animals↗

Monge: The Verriest lecture, Lyon, July 2005.

In 1789, when neither the physical basis of hue nor the retinal basis of color perception was established, the mathematician Gaspard Monte stated firmly that our color perceptions do not depend on the absolute value of the physical variable, but are influenced by the context and in particular by our estimate of the illuminant. He used this insight to explain color contrast effects and the Paradox of Monge (the desaturation of red objects seen through a red filter). He proposed that we can estimate the chromaticity of the illuminant in any scene because all surfaces reflect to us varying mixtures of (i) the body color and (ii) a specular component that represents the illuminant. He also realized that white objects have a special property: Provided that they are illuminated by a single illuminant, such objects exhibit no variation in chromaticity across their surface. Thus at least one of the unique hues exists as an external reference on which observers can agree. It is suggested that other unique hues may also have a basis in the external world.

Aged↗