Prophylaxis reduces cytomegalovirus (CMV) disease, but is associated with increased costs and risks for side effects, viral resistance and late onset CMV disease. Preemptive therapy avoids drug costs but requires frequent monitoring and may not prevent complications of asymptomatic CMV replication. Kidney transplant recipients at risk for CMV (D+/R−, D+/R+, D−/R+) were randomized to prophylaxis (valganciclovir 900 mg q.d. for 100 days, n = 49) or preemptive therapy (900 mg b.i.d. for 21 days, n = 49) for CMV DNAemia (CMV DNA level >2000 copies/mL in ≥ 1 whole blood specimens by quantitative PCR) assessed weekly for 16 weeks and at 5, 6, 9 and 12 months. More patients in the preemptive group, 29 (59%) than in the prophylaxis group, 14 (29%) developed CMV DNAemia, p = 0.004. Late onset of CMV DNAemia (>100 days after transplant) occurred in 11 (24%) randomized to prophylaxis, and none randomized to preemptive therapy. Symptomatic infection occurred in five patients, four (3 D+/R− and 1 D+/R+) in the prophylactic group and one (D+/R−) in the preemptive group. Peak CMV levels were highest in the D+/R− patients. Both strategies were effective in preventing symptomatic CMV. Overall costs were similar and insensitive to wide fluctuations in costs of either monitoring or drug.

Bacterial histidine kinases transduce extracellular signals into the cytoplasm. Most stimuli are chemically undefined; therefore, despite intensive study, signal recognition mechanisms remain mysterious. We exploit the fact that quorum-sensing signals are known molecules to identify mutants in the Vibrio cholerae quorum-sensing receptor CqsS that display altered responses to natural and synthetic ligands. Using this chemical-genetics approach, we assign particular amino acids of the CqsS sensor to particular roles in recognition of the native ligand, CAI-1 (S-3 hydroxytridecan-4-one) as well as ligand analogues. Amino acids W104 and S107 dictate receptor preference for the carbon-3 moiety. Residues F162 and C170 specify ligand head size and tail length, respectively. By combining mutations, we can build CqsS receptors responsive to ligand analogues altered at both the head and tail. We suggest that rationally designed ligands can be employed to study, and ultimately to control, histidine kinase activity.agonist | antagonist | quorum-sensing | two-component protein

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Thymoglobulin was associated with higher event-free survival, graft survival, and freedom from rejection without increased PTLD or CMV disease at 5 years compared with Atgam. The prolonged and profound lymphopenia may contribute to the long-term results associated with Thymoglobulin.

The advent of new laboratory methods and noninvasive imaging modalities has extended the diagnostic possibilities in normal individuals. This article elaborates the new options for the assessment of stroke risk offered by these techniques. In this context we present the Austrian Stroke Prevention Study, which is the first prospective long-term investigation of normals that includes Doppler sonography, magnetic resonance imaging and single photon emission computed tomography. The design, utility and limitations of this study are discussed.

Endovascular treatment of wide-neck MCA and basilar apex aneurysms resulted in a core lab adjudicated RR1 occlusion rate of 30.6%. Self-reported results at follow-up favour better angiographic outcomes, with OR 1.75 (95% CI 1.08 to 2.83). These data demonstrate the need for novel endovascular devices specifically designed to treat complex intracranial aneurysms, as well as the importance of core lab adjudication in assessing outcomes in such a trial.

Tacrolimus a macrolide immunosuppressant that is routinely given in two equally divided doses every 12 h. However, the time-dependent pharmacokinetics of tacrolimus suggest that once daily morning administration of tacrolimus may produce appropriate drug exposure. The purpose of this pilot study was to compare the pharmacokinetics and safety of twice vs. once daily administration of tacrolimus in stable kidney transplant recipients. Steady-state tacrolimus pharmacokinetic parameters were estimated on two occasions in an open-label, three-arm, two-period sequential study: twice daily dosing (Phase I) and once daily dosing (Phase II). In phase II, 18 patients were assigned to one of three arms: those taking 67%, 85% and 100% of their total twice daily dose once in the morning. In phase I, the mean area under the blood concentration-time curve (AUC) was higher after the morning dose, AUC 0-12 117 ± 40 vs. AUC 12-24 97 ± 30 ng/h/mL, p = = 0.012. In the 85% Group, the mean AUC ratio between twice and once daily was 1.0 (95% CI, 0.9-1.1) which predicted the best conversion ratio. Tacrolimus given once daily in the morning, at 85% of the twice daily dose, provides safe and equivalent drug exposure to twice daily dosing. This convenient dosing schedule may help to increase compliance and lower costs.

Serum sickness after rabbit anti-thymocyte globulin (ATG) has a reported incidence of 7–27% in kidney transplant patients. We describe four patients with previous exposure to rabbits who developed serum sickness after primary rabbit ATG induction. All patients presented with jaw pain. Three of four patients treated with plasmapheresis and steroids had prompt recovery and one patient treated with steroids had slower recovery. We performed a telephone interview of 214 patients contemporaneously transplanted between November 2006 and July 2008 regarding rabbit exposure. More than half of the patients had some type of previous rabbit exposure. There was a suggestion that patients with serum sickness were more frequently exposed to rabbits than those without. Jaw pain appears to be a hallmark symptom and treatment with plasmapheresis and steroids relieves symptoms more rapidly than steroids alone.