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Background/aim: Anterior teeth are prone to traumatic dental injuries (TDIs). Although a number of techniques ranging from original tooth fragment reattachment (TFR) to direct composite restoration (DCR) can be used to restore uncomplicated crown fractures, there is no consensus on which method is best. The purpose of this study was to investigate the fracture resistance of bovine incisors restored by two different techniques (TFR and DCR) in three different fracture models., Materials and Methods: Sixty extracted bovine lower incisors were randomly divided into three groups (n = 20). Angle, oblique, or transverse sections of all the teeth in a group were prepared by using a disk. The cut surfaces were scanned, and the cross-sectional areas (CSA) of the enamel and dentin were measured. Half the teeth in each group were restored by DCR (n = 10) and the other half by TFR (n = 10). The forces required to fracture the restored teeth were then measured using a Universal testing machine, and the fracture modes were analyzed (cohesive, adhesive, or mixed)., Results: No statistically significant differences between the TFR and DCR restorations were detected for total and enamel CSAs in any of the restoration shapes (p > .067). The fracture forces required to break DCR angle and transverse restorations were significantly greater than for the corresponding shapes restored with TFR (p < .033). However, the difference in the forces needed to fracture oblique section restorations by DCR or TFR was not statistically significant (p = .239), despite a similar trend (143.4 ± 51 N and 120.9 ± 25 N, respectively)., Conclusion: This study revealed that a greater force is required to fracture teeth restored by the DCR than by the TFR technique, especially for a transverse section. This demonstrates that restoring a fractured tooth provides a superior outcome compared to reattaching the fractured fragment., (© 2023 The Authors. Dental Traumatology published by John Wiley & Sons Ltd.)

SRL has been increasingly used in renal transplantation, but limited sampling approaches for estimation of AUC remain elusive. A post-hoc analysis of 94 PK profiles in 75 patients from four previous studies was performed to generate limited sampling approaches for approximation of AUC based on two to four time points for both BID and OD SRL dosing. AUC was calculated using the trapezoid rule. Stepwise linear regression was performed to generate an abbreviated AUC from the limited sampling approaches. For BID dosing, complete AUC had a strong correlation with the trough levels (r(2) = 0.882, p < 0.0001) and with C2 level (r(2) = 0.9025, p < 0.0001). A three-point and a four-point limited sampling approach showed improved agreement with complete AUC compared with single-point sampling. A convenient and accurate (r(2) = 0.992) four-point limited sampling approach reads: AUC = 10;(1.085 + 0.117 x log C0 + 0.164 x log C1-0.131 x log C2 + 0.823 x log C4). Similarly, complete AUC had a statistically significant correlation with the trough levels (r(2) = 0.549, p < 0.0001) and with C2 level (r(2) = 0.716, p < 0.0001) for OD dosing. The estimation of AUC for OD dosing was improved over single-point sampling (r(2) = 0.951) using the formula: AUC = 10;(1.100 + 0.115 x log C0 + 0.803 x log C4). This study represented the first limited sampling approach for SRL. Further studies are required to determine the optimal SRL target AUC.

We have previously reported sirolimus (SRL) pharmacokinetics (PK) in pediatric renal transplant recipients on a calcineurin inhibitor (CNI)-free protocol. We now report pediatric SRL PK in pediatric renal transplant patients receiving SRL + CNI. SRL was dosed to achieve target trough levels between 10 and 20 ng/mL. We performed 49 SRL PK profiles in pediatric renal transplant recipients receiving SRL in combination with either cyclosporine (CsA; 25 profiles), or tacrolimus (TCL; 24 profiles). Ten of the SRL + TCL profiles were obtained from children receiving SRL on a b.i.d. dosing regimen. All other SRL profiles were q.d. regimens. We calculated, the maximum concentration (C(max)), AUC, apparent clearance (aCL; dose/AUC) for dose in mg/m(2), and mean residence time (MRT). SRL levels were measured at 6 and 7 time points for b.i.d. and q.d. dosing, respectively. Regression analysis of SRL trough values vs. AUC showed good correlation in the SRL q.d. + CsA, SRL q.d. + TCL, and SRL b.i.d. + TCL groups (r(2) = 0.95, 0.68, and 0.44, respectively). SRL aCL corrected for body surface area was higher in children aged 0-5 yr receiving SRL with either CsA or TCL. SRL dosing schedule should be tailored to each patient. Higher SRL aCL may be present in younger children when administered with CNI.

The field of proteomics is developing at a rapid pace in the post-genome era. Translational proteomics investigations aim to apply a combination of established methods and new technologies to learn about protein expression profiles predictive of clinical events, therapeutic response, and underlying mechanisms. However, in contrast to genetic studies and in parallel with gene expression studies, the dynamic nature of the proteome in conjunction with the challenges of accounting for post-translational modifications requires the translational proteomics investigator to understand the strengths and limitations of proteomics approaches. In this review, we provide an overview of proteomics approaches and techniques, and proteomics informatics for clinical transplantation investigators. We also review recent publications pertaining to transplantation proteomics, and discuss the implications and utility of urine proteomics for non-invasive investigation of transplant outcomes.

Idiopathic nephrotic syndrome is the most common glomerular disorder of childhood. Recurrence of nephrotic syndrome immediately following renal transplantation is rapid, results in a high rate of graft loss, and represents the most severe form of nephrotic syndrome. This review discusses the molecular heterogeneity of pediatric nephrotic syndrome across the spectrum of disease activity. A schema is offered for a molecular approach to pediatric nephrotic syndrome, including immune-mediated and structural/genetic factors., (Copyright 2004 Blackwell Munksgaard)

Immunosuppression with SRL may provide an opportunity to avoid long-term exposure to the nephrotoxicity of CNI. Thus, we have initiated an experimental protocol of IL-2r antibody induction, prednisone, MMF and SRL in pediatric renal transplant recipients (median age 15.5 yr, IQR 8.5, range 1.3-21.7). The recipients were treated with daclizumab every 2 wk for the first 2 months, prednisone on a tapering schedule, MMF at 1200 mg/m(2)/day and SRL given b.i.d. The SRL was dosed to achieve defined target whole blood 12-h trough levels. We performed 24 SRL PK profiles in 13 stable pediatric renal transplant recipients at 1 and 3 months post-transplant. Half-life (T(1/2)) and terminal T(1/2) were 9.7 (7.1-24.6) and 10.8 (4.4-95.2) hours (median, range) respectively at month 1, and were 9.6 (5-17.8) and 12.1 (4.7-71.0) hours respectively at month 3. SRL trough levels correlated with AUC (r(2) = 0.84, p < 0.001). There was no relationship between SRL and mycophenolic acid (MPA) AUC values (r(2) = 0.04). During the first 3 months post-transplant only one patient experienced severe neutropenia and another patient had subclinical (histologic) evidence of a mild acute rejection episode with no change in renal function. We conclude that the T(1/2) of SRL in pediatric renal transplant recipients not treated with CNI is much shorter than what has been reported for adults, due to rapid metabolism. We conclude that children require SRL dosing every 12 h, higher doses and frequent drug monitoring to achieve target SRL concentrations.

Recurrence of nephrotic syndrome (NS) after transplantation (Tx) occurs in 20-50% of renal transplant recipients, with a median time to recurrence of 14 days and a 50% rate of graft loss. We performed a retrospective analysis of 22 pediatric patients with NS who received renal transplants at the Children's Hospital, Boston, between 1982 and 1999. During the first 14 days following Tx, 13 (59%) patients developed clinical recurrent nephrotic syndrome (RNS). RNS developed in 50% of living donor recipients and in 70% of cadaveric donor recipients (p= non-significant). Seven of the 13 patients with RNS were treated with plasmapheresis, while six received standard immunosuppressive induction therapy only. Two of the seven treated patients and one of the six untreated patients lost their grafts to RNS, yielding a total RNS graft loss rate of 23%. However, patients with RNS who achieved remission had significantly higher cumulative graft survival at 5 yr than did RNS patients who did not achieve remission (p< 0.001). Overall cumulative graft survival at 5 yr was not significantly different between the two groups: 67% in those with non-recurrent nephrotic syndrome (NRNS) vs. 64% in those with RNS, p= non-significant. We conclude that successful reversal of early RNS improves long-term graft survival in pediatric RNS. Multi-center studies are sorely needed to develop novel, less toxic therapies for native and recurrent NS.