Death with graft function in elderly patients after cadaveric renal transplantation: effect of waiting time.

Survival after kidney transplantation is better than on the waiting list, even in the elderly. However, the effects of a prolonged waiting time for an organ on death with graft function have not been critically examined in this patient group. We conducted a single-center retrospective analysis of our cadaveric renal transplant experience in patients older than 60 years who received a kidney between January 1, 1990 and December 31, 2003. Besides waiting time, the effects of recipient age, gender, and diabetes were also examined. Cox proportional hazards analysis using patient death as a time-dependent outcome was used to estimate the hazard ratio of death posttransplantation. Using Kaplan-Meier survival methodology, patients with waiting times < or =5 years had significantly better survival times posttransplantation compared with those with waiting times >5 years (6.2 vs 2.8 years; P <.001). Each year of waiting was associated with hazard ratio 1.16 (95% confidence interval [CI], 1.06-1.27) for death. Prolonged waiting time on dialysis is deleterious to patient survival in recipients older than 60 years at transplantation. Early transplantation thus should be strongly encouraged in this group of patients.

Effect of tacrine on EEG slowing in the rat: enhancement by concurrent monoamine therapy.

A dominant electrophysiological characteristic of Alzheimer's disease (AD) is the loss of desynchronized EEG activity and shift toward low-frequency EEG synchronization. In rats, similar EEG changes resulted from administering the anti-cholinergic scopolamine (1 mg/kg) and the monoamine depletor reserpine (10 mg/kg); amplitude increases between 0.5-20 Hz, with the delta (0.5-4 Hz) and theta (4-8 Hz) bands affected most severely. The acetylcholinesterase inhibitor tacrine, at doses between 10 and 20 mg/kg, reversed these EEG changes; co-administration of tacrine and the noradrenaline-serotonin reuptake inhibitor imipramine (10 mg/kg) enhanced tacrine's action to suppress delta activity. Co-administration of tacrine and the monoamine-oxidase inhibitor pargyline (20 mg/kg) enhanced EEG restoration by tacrine in all frequency bands between 0.5 to 20 Hz, but co-administration of the selective serotonin reuptake inhibitor fluoxetine (2 mg/kg) was ineffective. These results show that some drug therapies aimed at concurrently stimulating cholinergic and monoaminergic neurotransmission are more effective in reversing EEG slowing than cholinergic therapy alone. Significant monoaminergic deficits occur in Alzheimer's disease, in addition to the atrophy of cholinergic neurons. Thus, combined cholinergic-monoaminergic therapy may provide an enhanced restoration of cortical functioning, in addition to limiting the required treatment dose of cholinesterase inhibitors.