Prophylactic oral ganciclovir compared with deferred therapy for control of cytomegalovirus in renal transplant recipients.

BACKGROUND: Treatment with prophylactic oral acyclovir, intravenous ganciclovir, or immunoglobulins to prevent cytomegalovirus (CMV) infection and disease in renal transplantation is associated with variable efficacy and significant expense. We studied control of CMV in renal transplant recipients using either prophylactic oral ganciclovir or deferred therapy with intensive monitoring with polymerase chain reaction (PCR) analysis. METHODS: Forty-two recipients were followed for 6 months after transplantation. Ganciclovir (1000 mg p.o. t.i.d.; n=19) or acyclovir (200 mg p.o. b.i.d.; n=23) was begun at transplantation and continued for 12 weeks. PCR for CMV was performed on buffy-coat specimens every week for 15 weeks and at months 5 and 6. RESULTS: No patients in the ganciclovir group, compared with 14 of 23 patients (61%) in the deferred-therapy group (P<0.0001), developed CMV disease during the first 12 weeks. In the ganciclovir group, 4 of 19 patients (21%) subsequently experienced 5 episodes, whereas 14 patients in the deferred-therapy group experienced 18 episodes (P=0.013 for subjects and P=0.026 for episodes). The time to disease was also delayed in the ganciclovir group compared with the deferred-therapy group (133+/-17 days vs. 51+/-7 days; P<0.0001). Oral ganciclovir also prevented CMV viremia during prophylaxis (2/19 patients [11%] vs. 23/23 patients [100%]). Time to CMV viremia was delayed in the ganciclovir group; however, 13/19 patients (68%) ultimately showed PCR evidence for CMV viremia (P=0.005). CONCLUSIONS: An initial 12-week course of oral ganciclovir prevents CMV disease and infection in renal transplant recipients during prophylaxis, and the benefits persist after discontinuation.

Pharmacology of volume regulation following hypotonicity-induced cell swelling in clonal N1E115 neuroblastoma cells.

When exposed to hypotonic solutions, clonal N1E115 neuroblastoma cells initially swell and later undergo a regulatory volume decrease (RVD). We studied the effects of a variety of transport inhibitors on the time course of cross-sectional area of N1E115 cells exposed to a solution of reduced osmolarity (pi = 186 mosm). Application to the bath of either: (i) blockers of net K efflux through K channels (e.g. isotonic KCl or 20 mM TEA); or (ii) blockers of net efflux through anion channels (e.g. isotonic methanesulfonate, 10 microM DIDS or 100 microM IAA-94) all prevent RVD. In contrast, ouabain (a Na+/K+ pump blocker), bumetanide (a Na+/K+/Cl- cotransporter blocker) and SITS (a HCO3-/Cl- exchange blocker) do not. These data support the involvement of these channels over pumps or exchangers in solute exit during RVD. Only variable block of RVD was achieved using blockers of stretch activated non-selective cation C+ (SA) channels (i.e., amiloride and gadolinium, Gd3+) or a membrane permeant Ca chelator (BAPTA-AM) suggesting that neither the opening of C+ (SA) channels nor a global rise in cytosolic Ca2+ is critical for triggering RVD.