Introduction: After kidney transplantation, rejection and drug-related toxicity occur despite tacrolimus whole blood pre-dose concentrations ([Tac](blood)) being within the target range. The... Show moreIntroduction: After kidney transplantation, rejection and drug-related toxicity occur despite tacrolimus whole blood pre-dose concentrations ([Tac](blood)) being within the target range. The tacrolimus concentration within peripheral blood mononuclear cells ([Tac](cells)) might correlate better with clinical outcomes. The aim of this study was to investigate the correlation between [Tac](blood) and [Tac](cells), the evolution of [Tac](cells) and the [Tac](cells)/[Tac](blood) ratio, and to assess the relationship between tacrolimus concentrations and the occurrence of rejection. Methods: In this prospective study, samples for the measurement of [Tac](blood) and [Tac](cells) were collected on days 3 and 10 after kidney transplantation, and on the morning of a for-cause kidney transplant biopsy. Biopsies were reviewed according to the Banff 2019 update. Results: Eighty-three [Tac](cells) samples were measured of 44 kidney transplant recipients. The correlation between [Tac](cells) and [Tac](blood) was poor (Pearson's r = 0.56 (day 3); r = 0.20 (day 10)). Both the dose-corrected [Tac](cells) and the [Tac](cells)/[Tac](blood) ratio were not significantly different between days 3 and 10, and the median inter-occasion variability of the dose-corrected [Tac](cells) and the [Tac](cells)/[Tac](blood) ratio were 19.4% and 23.4%, respectively (n = 24). Neither [Tac](cells), [Tac](blood), nor the [Tac](cells)/[Tac](blood) ratio were significantly different between patients with biopsy-proven acute rejection (n = 4) and patients with acute tubular necrosis (n = 4) or a cancelled biopsy (n = 9; p > 0.05). Conclusion: Tacrolimus exposure and distribution appeared stable in the early phase after transplantation. [Tac](cells) was not significantly associated with the occurrence of rejection. A possible explanation for these results might be related to the low number of patients included in this study and also due to the fact that PBMCs are not a specific enough matrix to monitor tacrolimus concentrations. Show less
Velde, D. van de; Schiller, N.O.; Levelt, C.C.; Heuven, V.J.J.P. van; Beers, M.; Briaire, J.; Frijns, J.H.M. 2018
The perception and production of emotional and linguistic (focus) prosody were compared in children with cochlear implants (CI) and normally hearing (NH) peers. Thirteen CI and thirteen hearing-age... Show moreThe perception and production of emotional and linguistic (focus) prosody were compared in children with cochlear implants (CI) and normally hearing (NH) peers. Thirteen CI and thirteen hearing-age-matched school-aged NH children were tested, as baseline, on non-verbal emotion understanding, non-word repetition, and stimulus identification and naming. Main tests were verbal emotion discrimination, verbal focus position discrimination, acted emotion production, and focus production. Productions were evaluated by NH adult Dutch listeners. All scores between groups were comparable, except a lower score for the CI group for non-word repetition. Emotional prosody perception and production scores correlated weakly for CI children but were uncorrelated for NH children. In general, hearing age weakly predicted emotion production but not perception. Non-verbal emotional (but not linguistic) understanding predicted CI children's (but not controls’) emotion perception and production. In conclusion, increasing time in sound might facilitate vocal emotional expression, possibly requiring independently maturing emotion perception skills. Show less
