BACKGROUND:The aim of this study was to evaluate whether a deficit in vitamin D (VD) is associated with an increased risk of recurrent acute otitis media (AOM) and whether VD supplementation is effective in reducing the number of AOM episodes in otitis-prone children.METHODS:A total of 116 children with a history of recurrent AOM (≥3 episodes in preceding 6 months or ≥4 episodes in preceding 12 months) were prospectively and blindly randomized to receive oral VD 1000 IU/d or placebo for 4 months. Episodes of AOM were monitored for 6 months.RESULTS:Fifty-eight children received placebo and 58 with similar characteristics were treated with VD. The number of children experiencing ≥1 AOM episode during the study period was significantly lower in the treatment group (26 versus 38; P = 0.03). There was a marked difference in the number of children who developed uncomplicated AOM (P < 0.001), but no difference in the number of children with ≥1 episode of spontaneous otorrhea. The likelihood of AOM was significantly reduced in the patients whose serum VD concentrations were ≥30 ng/mL.CONCLUSIONS:VD hypovitaminosis is common in children with recurrent AOM and associated with an increase in the occurrence of AOM when serum 25(OH)D levels are <30 ng/mL. The administration of VD in a dosage of 1000 IU/d restores serum values of ≥30 ng/mL in most cases and is associated with a significant reduction in the risk of uncomplicated AOM.

As vitamin D (VD) has a significant regulatory effect on innate and adaptive immunity, the aim of this prospective, randomized, single-blinded, placebo-controlled study was to measure the impact of VD administration on the immune response to trivalent influenza vaccination (TIV). A total of 116 children (61 males, 52.6%; mean age 3.0 ± 1.0 y) with a history of recurrent acute otitis media (AOM), who had not been previously vaccinated against influenza, were randomized to receive daily VD 1,000 IU or placebo by mouth for four months. All of them received two doses of TIV (Fluarix, GlaxoSmithKline Biologicals) one month apart, with the first dose administered when VD supplementation was started. There was no difference in seroconversion or seroprotection rates, or antibody titers, in relation to any of the three influenza vaccine antigens between the VD and placebo groups, independently of baseline and post-treatment VD levels. The safety profile was also similar in the two groups. These data indicate that the daily administration of VD 1,000 IU for four months from the time of the injection of the first dose of TIV does not significantly modify the antibody response evoked by influenza vaccine.

This longitudinal study assessed the influence of post-transplant clinical and therapeutic variables in 50 kidney transplant recipients aged 2-19 yr receiving a triple immunosuppressive regimen consisting of cyclosporine microemulsion (CsA), steroids and MMF (300-400 mg/m(2) body surface area twice daily), the full pharmacokinetic profile (10 points) of which was investigated on post-transplant days 6, 30, 180 and 360. Total plasma MPA was measured by Enzyme Multiplied Immunoassay Technique. CsA therapeutic drug monitoring (TDM) was performed via C2 blood monitoring, while MPA TDM via C0. MPA Cmax, tmax, AUC0-12 and AUC0-4 pharmacokinetic profile changed significantly during the first post-transplant year. C0 was a poor predictor of the total MPA exposure [as measured by the area under the concentration-time curve AUC)], while a truncated AUC was a good surrogate of the 12-h profile (r = 0.91; p < 0.001) Graft function and cyclosporine therapy influenced MPA pharmacokinetics, as shown by the univariate and multivariate analyses. We conclude that because after transplantation MPA exposure varied over time, a strict TDM is advisable in the pediatric population.

BACKGROUND:CYP3A5 gene polymorphism has been shown to influence tacrolimus (TAC) blood concentration and dose requirement in adult kidney transplant patients. The aim was to analyze retrospectively the modification induced by CYP3A5 gene polymorphism on TAC's pharmacokinetic parameters obtained from 26 adolescents receiving TAC as their main immunosuppressive drug.MATERIAL/METHODS:The adolescent kidney transplant patients were genotyped for CYP3A5*3 and grouped accordingly. TAC dose, blood levels, and dose-normalized TAC blood concentration and volume of distribution obtained at different post-transplant periods during the first post-transplant year were correlated with the corresponding genotype.RESULTS:During the first three months post-transplant, heterozygotes (CYP3A5*1/*3) displayed a lower TAC blood concentration than homozygotes (CYP3A5*3/*3) (at 1 month: 7.8+/-2.1 vs. 13.4+/-6 ng/ml, p=0.007) despite a therapeutic monitoring strategy. Between 3-12 months post-transplant, TAC blood concentration was comparable between the two groups, but a two-fold increase in the daily drug dose was necessary for the heterozygotes (at 6 months: 0.23+/-0.1 vs. 0.13+/-0.06 mg/kg, p=0.04). The dose-normalized TAC concentration [(ng/ml)/(mg/kg)] was significantly lower in patients displaying the CYP3A5*1/*3 polymorphism (at 2 weeks: 33+/-2.16 vs. 71.1+/-37.8, p=0.01; 6 months: 35.4+/-12.9 vs. 85.2+/-58.9, p=0.01). At the same time, the volume of distribution of the drug in the latter group was distinctly increased for the entire post-transplant year (at 6 months: 1.79+/-0.42 vs. 0.73+/-0.5 l/kg, p=0.001).CONCLUSIONS:The great influence of CYP3A5 on the pharmacokinetics and pharmacodynamics of TAC in young transplant recipients suggests the need for pre-transplant screening of this polymorphism to improve TAC therapy.

Myśliwiec M. The periodontal status of pre-dialysis chronic kidney disease and maintenance dialysis patients. Nephrol Dial Transplant 2007; 22: 457–464 3. Trzonkowski P, Mysliwska J, De bska-S?lizień A et al. Longterm therapy with recombinant human erythropoietin decreases percentage of CD 152þ lymphocytes in primary glomerulonephritis haemodialysis patients. Nephrol Dial Transplant 2002; 17: 1070–1080 4. Tyrzyk S, Sadlak-Nowicka J, Ke dzia A, Bochniak M, Szumska-Tyrzyk B, Rutkowski P. Clinical and mycological examinations of oral mucosa in cyclosporine A treated patients after renal transplantation. Przegl Lek 2004; 61: 467–472 5. Tyrzyk S, Sadlak-Nowicka J, Ke dzia A, Bochniak M, Rutkowski P. Proposal of a periodontal preventive and treatment scheme for patients before and after renal transplantation receiving cyclosporine A. Dent Med Probl 2006; 43: 483–491 6. Stellingsma C, Vissink A, Meijer HJA, Kuiper C, Raghoebar GM. Implantology and the severely resorbed edentulous mandible. Crit Rev Oral Biol Med 2004; 15: 240–248 7. Wojtowicz A, Grabowska K, Kukula K et al. Densitometric examination of male patients with renal osteodystrophy. Prot Stom 2002; 52: 195–201 8. Kukula K, Wojtowicz A, Dijakiewicz M et al. The linear rediometric analysis of the jaws in renal osteodystrophy: introduction to implanto-prosthodontic treatment. Prot Stom 2005; 55: 336–343 9. Wojtowicz A, Dijakiewicz M, Wandzel B et al. The evaluation of mineral crystallinity of mandibular bone tissue using electron paramagnetic resonance (EPR) in patients suffering from renal osteodystrophy. Przegl Lek 2006; 63: 759–761 10. Dijakiewicz M, Wojtowicz A. Problems and algorithm of dental procedures in patients on renal replacement therapy. In: Rutkowski B, ed. Dialysis in Medical Practice, MAKmedia, Gdańsk: 2004

(r1⁄4 0.495; P1⁄4 0.024). There were no relationships between IL-6 changes and the main mineral metabolism related parameters. Our results agree with previous experimental findings [4] and point to the efficacy of calcimimetic drugs for the control of uraemic SHP. It was unexpected that 6 months of cinacalcet treatment resulted in highly significant increases in OPG and decreases in Fetuin-A serum levels. OPG, a cytokine produced and secreted mainly by osteoblasts, has been claimed to play an as yet undefined role in the vascular calcification process. Although a protective effect of increased OPG levels on vascular calcification has been suggested, higher OPG serum levels have been linked to an increased extent of arterial wall calcification, increased mortality rates in uraemic patients, and most importantly, with increased mortality in dialysis patients [3,5]. The clinical significance of the OPG increase observed in our patients and its potential effects on the vascular calcification process cannot be drawn from our data. Interestingly, OPG increases were significantly correlated with the degree of reduction in c-Ca levels. In association with the OPG increases, cinacalcet treatment also caused significant decreases in Fetuin-A levels without changes in IL-6, indicating no change in the inflammatory state in our patients. The Fetuin-A reduction was significantly related to PTH decreases. Previous studies have emphasized an association between low Fetuin-A levels with both increased vascular calcification and cardiovascular mortality [2,6]. From our data, we cannot determine whether the Fetuin-A decrease represents a real increase in risk for the calcification process, or whether it is the consequence of a reduced demand for a feedback defence mechanism, which may be secondary to improved mineral metabolism, by cinacalcet, that reduces the pro-calcification burden. This possibility was proposed in non-dialysed diabetic nephropathy patients [7]. Although we are aware of the main limitation of this preliminary study, the highly significant changes in both OPG and Fetuin-A levels observed in our patients provide a stimulus and starting point for further research in this field.