The authors analyzed the relationship between patient age and the final outcome in a series of 810 patients aged 14 years or older who were consecutively admitted between 1987 and 1996 after suffering a severe closed head injury. The most relevant clinico-radiological variables were prospectively collected in a Data Bank. Stratified and logistic regression analyses were performed in order to assess the influence of age on adverse outcome and the interaction between patient age and other prognostic indicators. Our results reaffirm that the adverse outcome rate increases steadily with age in severe head injured patients and that age effect on outcome is independent of other prognostic variables. The odds of having an adverse outcome increases significantly over 35 years of age being 10 times higher in patients older than 65 years as compared to those aged 15-25 years (reference age group). The adverse influence of an advanced age on the final outcome has not yet been satisfactorily explained but an older brain may have an impaired ability to recover after a pathological insult as compared to a younger one.

SummaryReperfusion injury remains one of the major problems in transplantation. Repair from ischaemic acute renal failure (ARF) involves stimulation of tubular epithelial cell proliferation. The aim of this exploratory study was to evaluate the effects of preconditioning donor animals with rapamycin and tacrolimus to prevent ischaemia-reperfusion (I/R) injury. Twelve hours before nephrectomy, the donor animals received immunosuppressive drugs. The animals were divided into four groups, as follows: group 1 control: no treatment; group 2: rapamycin (2 mg/kg); group 3 FK506 (0, 3 mg/kg); and group 4: FK506 (0, 3 mg/kg) plus rapamycin (2 mg/kg). The left kidney was removed and after 3 h of cold ischaemia, the graft was transplanted. Twentyfour hours after transplant, the kidney was recovered for histological analysis and cytokine expression. Preconditioning treatment with rapamycin or tacrolimus significantly reduced blood urea nitrogen and creatinine compared with control [blood urea nitrogen (BUN): P < 0·001 versus control and creatinine: P < 0·001 versus control]. A further decrease was observed when rapamycin was combined with tacrolimus. Acute tubular necrosis was decreased significantly in donors treated with immunosuppressants compared with the control group (P < 0·001 versus control). Moreover, the number of apoptotic nuclei in the control group was higher compared with the treated groups (P < 0·001 versus control). Surprisingly, only rapamycin preconditioning treatment increased anti-apoptotic Bcl2 levels (P < 0·001). Finally, inflammatory cytokines, such as tumour necrosis factor (TNF)-a and interleukin (IL)-6, showed lower levels in the graft of those animals that had been pretreated with rapamycin or tacrolimus. This exploratory study demonstrates that preconditioning donor animals with rapamycin or tacrolimus improves clinical outcomes and reduce necrosis and apoptosis in kidney I/R injury.

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