Expression of common gamma chain signalling cytokines and their receptors distinguishes rejection from tolerance in a rat organ transplant model.

BACKGROUND: Signalling through the cytokine common γ chain (γc) is crucial for survival of activated T cells. In its absence, severe combined immunodeficiency ensues and transplanted tissues are not rejected. METHODS: To determine whether differences in the availability of γc signalling cytokines correlate with rejection or acceptance, we examined expression of all γc signalling components in organs transplanted between PVG donors and DA recipients. In this combination hearts or kidneys are rejected in <10 days while livers survive >100 days. Expression of the γc cytokines IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 and their receptors γc, IL-2Rα, IL-2Rß/IL-15Rß, IL-4Rα, IL-7Rα, IL-9Rα, IL-15Rα and IL-21Rα was determined by real-time PCR pre-transplant and on days 3, 5 and 7 after transplantation. RESULTS: Most increased after transplantation, although there were significantly lower levels of IL-2, IL-2Rα, IL-4 and IL-15Rα in tolerant livers compared to rejecting hearts or kidneys. IL-9 was only expressed in normal kidneys and decreased during rejection. IL-15 was constitutively expressed and did not change after transplantation. IL-21 and IL-21R increased in all transplanted organs to a similar extent. IL-7Rα in liver was considerably increased compared with heart or kidney, consistent with its known inverse relationship to global levels of γc signalling. CONCLUSIONS: In transplanted livers, acceptance is associated with low levels of all γc cytokines or receptors except IL-21. This is consistent with "dilution" of γc cytokines from a finite clone size of alloreactive T cells in livers, which are ten times larger than kidneys or hearts.

The 2009 Sydney shark attacks: case series and literature review.

BACKGROUND: There were 59 unprovoked shark attacks worldwide in 2008. Twelve of these occurred in Australia, ranking it as second only to the USA. In February 2009, two attacks occurred within 72 h in Sydney, Australia. METHODS: The two patients involved survived severe limb trauma. Case 1 suffered bite trauma to the lower limb and hand and underwent staged debridement and early amputation. Case 2 presented with a hand severed at the level of the wrist that was initially replanted. However, it would succumb to progressive necrosis after 12 days. We discuss the aspects of these cases that contributed to the patients' survival and ultimately good functional outcomes. DISCUSSION: New paradigms for the management of major trauma patients have emerged over the last decade. We consider recent advances in the understanding of pre-hospital tourniquet use, rapid transit to the operating suite and damage control surgery, and examine how they impacted on the management of our patients. Very little is known about the microbiology of shark bites. Organisms from sea water, the patient's skin and the shark's mouth must all be considered when selecting appropriate antimicrobial prophylaxis. The planning of definitive surgery in severe limb trauma is dependent on the interactions of a number of factors including physical, psychological and social issues. The decision to ultimately replant or amputate the effected limb is best made in union with the patient and their family.