Mutations in dysferlin cause an inherited muscular dystrophy because of defective membrane repair. Three interacting partners of dysferlin are also implicated in membrane resealing: caveolin-3 (in limb girdle muscular dystrophy type 1C), annexin A1, and the newly identified protein mitsugumin 53 (MG53). Mitsugumin 53 accumulates at sites of membrane damage, and MG53-knockout mice display a progressive muscular dystrophy. This study explored the expression and localization of MG53 in human skeletal muscle, how membrane repair proteins are modulated in various forms of muscular dystrophy, and whether MG53 is a primary cause of human muscle disease. Mitsugumin 53 showed variable sarcolemmal and/or cytoplasmic immunolabeling in control human muscle and elevated levels in dystrophic patients. No pathogenic MG53 mutations were identified in 50 muscular dystrophy patients, suggesting that MG53 is unlikely to be a common cause of muscular dystrophy in Australia. Western blot analysis confirmed upregulation of MG53, as well as of dysferlin, annexin A1, and caveolin-3 to different degrees, in different muscular dystrophies. Importantly, MG53, annexin A1, and dysferlin localize to the t-tubule network and show enriched labeling at longitudinal tubules of the t-system in overstretch. Our results suggest that longitudinal tubules of the t-system may represent sites of physiological membrane damage targeted by this membrane repair complex.

A temporal association between hemodynamic dysfunction, myocardial edema, and increased aquaporin 1 expression was demonstrated. Cardiopulmonary bypass without ischemia was associated with minimal edema, negligible myocardial dysfunction, and static aquaporin expression. Ischemic reperfusion injury is the main cause of myocardial edema and myocardial dysfunction, but a causal relationship between edema and dysfunction remains to be proved.

The anaesthetic implications of mucolipidosis in three siblings is reported. Two of the three children e>;hibit marked difficulty with their airways under anaesthesia and all three have narrow tracheas. Surgery and anaesthesia should be undertaken with caution in patients with a mucolipidosis.

Changes in protein expression within the myocardial membrane were found in a clinically relevant model of pediatric cardiac surgery. Indicators of reduced performance, such as lower blood pressure and lower oxygen delivery, were lessened in association with the administration of the membrane protecting poloxamer 188. Poloxamer 188 was also associated with potentially beneficial changes in membrane protein expression, reduced capillary leakage, and less hemodilution.

The incidence of gastro-oesophageal reflux in children undergoing general anaesthesia has not previously been studied. Onehundred-and-twenty children (ASA Class 1-2) were studied intraoperatively using continuous oesophageal pH monitoring. The incidence of reflux was 2.5% (3 of 120). None of these three patients had an adverse respiratory event. There was no correlation between reflux and adverse respiratory events. Thirteen patients had minor respiratory events without evidence of acid reflux. Gastro-oesophageal reflux does occur in healthy paediatric patients having minor surgery, but was not a significant cause of the adverse respiratory events that occurred in our study.

Liver transplantation is an accepted modality of treatment in some patients with inborn errors of metabolism. We present a child with methylmalonic acidaemia who had successful liver transplantation. The pathophysiology, medical and anaesthetic managements are discussed.

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