Markers of operational immune tolerance after pediatric liver transplantation in patients under immunosuppression.

A prospective identification of the estimated 20-50% of pediatric LTX recipients developing operational tolerance would be of great clinical advantage. So far markers of immune tolerance - T-cell subpopulations or gene expression profiles - have been investigated only retrospectively in successfully weaned patients. Fifty children aged 8-265 months (median 89) were investigated 1-180 months (median 44) after LTX under ongoing immunosuppression. T-cell subpopulations were measured during regular post-transplant visits using FACS (Vδ1- vs. Vδ2-γδ-T cells and Tregs). A Vδ1/Vδ2-γδ-T-cell ratio ≥1.42 previously reported in operational tolerance was found in 12 of 50 (24%) patients. In analogy, a Treg count ≥44 per µL was found in 35 of 50 (70%) patients and a Treg proportion ≥2.23% of CD3(+) -T cells in 39 of 50 (78%) patients. Only 9 of 50 patients (18%) fulfilled both criteria. The parameters Vδ1/Vδ2-γδ-T-cell ratio and Tregs were not significantly correlated to each other or with donor type or immunosuppression. Vδ1/Vδ2-γδ-T-cell ratio was more stable in serial examinations compared with Treg analyses. The observed proportion of 18% pediatric LTX patients with potential operational tolerance is in accordance with previous reports. However, clinical experience shows that rejections may happen even after long-time weaning of immunosuppression. This suggests that operational tolerance is a dynamic process, with uncertain prediction by Vδ1/Vδ2-γδ-T-cell ratio and/or Tregs under immunosuppression.

Intensive playing leads to non-monosymptomatic enuresis in children with low prepulse inhibition.

AIM: Parents of children suffering from non-monosymptomatic enuresis (nmE) report their child wetting itself during intensive playing. As children with enuresis are characterized by reduced bladder control (measured as prepulse inhibition (PPI) of startle reflex), the hypothesis suggests that intensive playing leads to further decrease in control and consecutive wetting. Two questions are important: Does PPI change while concentrating? Is this difference more explicit in children with daytime incontinence? METHODS: Forty-four healthy children, 40 children with nmE and 37 with monosymptomatic enuresis (mE) were examined. PPI was measured while watching DVD and while playing Nintendo's Wii(®) , and calculated as percentage of the native startle response. RESULTS: All probands showed a relevant decrease in PPI: in relaxed state, the PPI of the controls was 54%; when concentrating, it fell to 34.5% (p = 0.014). The decrease in PPI in mE was from 66% to 51% (p = 0.008), and the decrease in PPI in nmE was from 29% to 21% (p = 0.125). CONCLUSION: While the decrease in PPI when playing was smallest in the group with nmE, overall PPI level was by far the lowest. The findings confirm the aetiology of enuresis through impaired 'sensori-motor gating' in children with nmE and provide a neurophysiologic correlate for wetting while playing.

Effects of desmopressin on the sleep of children suffering from enuresis.

AIM: To evaluate the effect of 1-desamino-8-D-Arginine Vasopressin (DDAVP) on sleep architecture and arousal reactions in children with primary monosymptomatic nocturnal enuresis (PME). METHODS: A prospective, placebo-controlled, randomized, double-blind, cross-over study was performed on children suffering from bed-wetting. Placebo and DDAVP were given for 7 days each after which an unattended home polysomnography (PSG) was recorded. After lifting the blinding, the PSGs were compared. RESULTS: A total of 20 children with PME, aged 6-15 years, were enrolled in the study. The number of wet nights decreased significantly with DDAVP treatment. Delta power, distribution of sleep stages, number of arousals, arousal index and the effect of arousals on sleep stages did not differ significantly. Bed-wetting occurred within each sleep stage and did not follow any particular pattern. In most cases, it was preceded by an arousal reaction, but no awakening occurred. CONCLUSION: DDAVP has no effect on the sleep architecture of children with PME when analysed by classical PSG, which is determined by collecting the electric activity of cortical neurons. Taking recent research findings into account, this supports the thesis that the disturbances causing PME occur at brain stem level and do not reach consciousness.

Maturation of prepulse inhibition (PPI) in childhood.

It is known that sensorimotor gating measured by the prepulse inhibition of the startle reflex (PPI) matures during childhood. Since certain disorders in children, for example, enuresis, show a significant loss in PPI, the PPI as a tool for investigating brainstem reflex control mechanism gains in importance. Therefore, it is crucial to know the natural course of PPI maturation in childhood. A total of 122 healthy children aged from 3-10 years and 10 healthy adults were examined. PPI was initiated by a 120 ms and a 60 ms prepulse and was measured by the EMG of M. orbicularis oculi. For the respective prepulse intervals, the PPI level in each age group increased from 3 to 9 or 10 years and showed a similar course. The findings confirm and extend knowledge about the maturation of PPI during childhood and emphasize the importance of age-dependent standard values when investigating PPI in children.