Emerging technologies for the prevention of dental caries. Are current methods of prevention sufficient for the high risk patient?

Fluorides and chlorhexidine are technologies that are 65 and 40 years old, respectively. This overview argues that current methods of caries prevention are not effective for the high caries risk patient. In this review examples, arguments and recommendations are provided to address the high caries risk patient that include: failure of comprehensive chemical modalities treatments to address the high caries risk patient; ecological alteration - would this be an effective approach?; and biomaterials and oral microbiome research to address the high caries risk patient.

Biological monitoring of a xenomaterial for grafting: an evaluation in critical-size calvarial defects

Our purpose was to evaluate the osteoconduction potential of mixed bovine bone (MBB) xenografts as an alternative for bone grafting of critical-size defects in the calvaria of rats. After surgery, in the time intervals of 1, 3, 6, and 9 months, rats were killed and their skulls collected, radiographed and histologically prepared for analysis. The data obtained from histological analysis reported that the particles of MBB did not promote an intense immunological response, evidencing its biocompatibility in rats. Our results clearly showed the interesting evidence that MBB was not completely reabsorbed at 9 months while a small amount of newly formed bone was deposited by osteoprogenitor cells bordering the defect. However, this discrete bone-forming stimulation was unable to regenerate the bone defect. Overall, our results suggest that the properties of MBB are not suitable for stimulating intense bone regeneration in critical bone defects in rats.

Implicit Taylor methods for stiff stochastic differential equations

In this paper we discuss implicit Taylor methods for stiff Ito stochastic differential equations. Based on the relationship between Ito stochastic integrals and backward stochastic integrals, we introduce three implicit Taylor methods: the implicit Euler-Taylor method with strong order 0.5, the implicit Milstein-Taylor method with strong order 1.0 and the implicit Taylor method with strong order 1.5. The mean-square stability properties of the implicit Euler-Taylor and Milstein-Taylor methods are much better than those of the corresponding semi-implicit Euler and Milstein methods and these two implicit methods can be used to solve stochastic differential equations which are stiff in both the deterministic and the stochastic components. Numerical results are reported to show the convergence properties and the stability properties of these three implicit Taylor methods. The stability analysis and numerical results show that the implicit Euler-Taylor and Milstein-Taylor methods are very promising methods for stiff stochastic differential equations.

Topological methods for some boundary value problems

We establish existence of solutions for a finite difference approximation to y = f(x, y, y ') on [0, 1], subject to nonlinear two-point Sturm-Liouville boundary conditions of the form g(i)(y(i),y ' (i)) = 0, i = 0, 1, assuming S satisfies one-sided growth bounds with respect to y '. (C) 2001 Elsevier Science Ltd. All rights reserved.

Stiffly accurate Runge-Kutta methods for stiff stochastic differential equations

In this paper we discuss implicit methods based on stiffly accurate Runge-Kutta methods and splitting techniques for solving Stratonovich stochastic differential equations (SDEs). Two splitting techniques: the balanced splitting technique and the deterministic splitting technique, are used in this paper. We construct a two-stage implicit Runge-Kutta method with strong order 1.0 which is corrected twice and no update is needed. The stability properties and numerical results show that this approach is suitable for solving stiff SDEs. (C) 2001 Elsevier Science B.V. All rights reserved.

A retrospective analysis of mycophenolic acid and cyclosporin concentrations with acute rejection in renal transplant recipients

Objectives: Although monitoring of cyclosporin (CsA) is standard clinical practice postrenal transplantation. mycophenolic acid (MPA) concentrations are not routinely measured. There is evidence that a relationship exists between MPA area under the concentration-time curve (AUC) and rejection. In this study, a retrospective analysis was undertaken of 27 adult renal transplant recipients. Methods: Patients received CsA and MPA therapy and had a four-point MPA AUC investigation. The relationship between MPA AUC performed in the first week after transplantation, as well as median trough cyclosporin concentrations, and clinical outcomes in the first month posttransplant were evaluated. Results: A total of 12 patients experienced biopsy proven rejection (44.4%) and 4 patients had gastrointestinal adverse events (14.8%). A statistically significant relationship was observed between the incidence of biopsy proven rejection and both MPA AUC (p = 0.02) and median trough CsA concentration (p = 0.008). No relationship between trough MPA concentration and rejection was observed (p = 0.21). Only 3 of 11 (27%) patients with an MPA AUC > 30 mg.h/L and a median trough CsA > 175 mug/L experienced acute rejection, compared with a 56% incidence of rejection for the remaining 16 patients. Patients who experienced adverse gastrointestinal events had significantly lower MPA AUC (p = 0.04), but median trough CsA concentrations were not significantly different (p = 0.24). Further, 3 of these 4 patients had rejection episodes. Conclusions: in addition to standard CsA monitoring, we propose further investigation of the use of a 4-point sampling strategy to predict MPA AUC in the first week posttransplant, which may facilitate optimization of mycophenolate mofetil dose at a rime when patients are most vulnerable to acute rejection. (C) 2001 The Canadian Society of Clinical Chemists. All rights reserved.

Population pharmacokinetics of perhexiline from very sparse, routine monitoring data

Using NONMEM, the population pharmacokinetics of perhexiline were studied in 88 patients (34 F, 54 M) who were being treated for refractory angina. Their mean +/- SD (range) age was 75 +/- 9.9 years (46-92), and the length of perhexiline treatment was 56 +/- 77 weeks (0.3-416). The sampling time after a dose was 14.1 +/- 21.4 hours (0.5-200), and the perhexiline plasma concentrations were 0.39 +/- 0.32 mg/L (0.03-1.56). A one-compartment model with first-order absorption was fitted to the data using the first-order (FO) approximation. The best model contained 2 subpopulations (obtained via the $MIXTURE subroutine) of 77 subjects (subgroup A) and 11 subjects (subgroup B) that had typical values for clearance (CL/F) of 21.8 L/h and 2.06 L/h, respectively. The volumes of distribution (V/F) were 1470 L and 260 L, respectively, which suggested a reduction in presystemic metabolism in subgroup B. The interindividual variability (CV%) was modeled logarithmically and for CL/F ranged from 69.1% (subgroup A) to 86.3% (subgroup B). The interindividual variability in V/F was 111%. The residual variability unexplained by the population model was 28.2%. These results confirm and extend the existing pharmacokinetic data on perhexiline, especially the bimodal distribution of CL/F manifested via an inherited deficiency in hepatic and extrahepatic CYP2D6 activity.

A proposal for developing a large patient population cohort for longterm safety monitoring in rheumatoid arthritis

This paper proposes the creation of an objectively acquired reference database to more accurately characterize the incidence and longterm risk of relatively infrequent, but serious, adverse events. Such a database would be maintained longitudinally to provide for ongoing comparison with new rheumatologic drug safety databases collecting the occurrences and treatments of rare events, We propose the establishment of product-specific registries to prospectively follow a cohort of patients with rheumatoid arthritis (RA) who receive newly approved therapies. In addition, a database is required of a much larger cohort of RA patients treated with multiple second line agents of sufficient size to enable case-controlled determinations of the relative incidence of rare but serious events in the treated (registry) versus the larger disease population, The number of patients necessary for agent-specific registries and a larger patient population adequate to supply a matched case-control cohort will depend upon estimates of the detectability of an increased incidence over background. We suggest a system to carry out this proposal that will involve an umbrella organization. responsible for establishment of this large patient cohort, envisioned to be drawn from around the world.