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BACKGROUND: Propacetamol is an acetaminophen prodrug that was available in Europe as an IV formu lation for the treatment of pain and fever for some time. One gram of propacetamol is hydrolyzed in blood to release 0.5 g of acetaminophen and pharmacologically inactive N,N-diethylglycine. OBJECTIVE: This study compared the antipyretic efficacy and tolerability of IV propacetamol and placebo after a single administration in children with acute fever of infectious origin. The study was performed in anticipation of an application for US registration. METHODS: This was a double-blind, placebo-controlled trial in which patients with a body temperature (tympanic probe) of 38.5 degrees C to 41 degrees C were randomized to receive propacetamol 30 mg/kg IV or a placebo of identical appearance, both administered as 15-minute infusions. Temperature was measured at baseline, 0.5 hour after drug administration, and hourly thereafter for 6 hours or until use of rescue medication. The primary efficacy variable was the change in body temperature at each evaluation time compared with baseline. Secondary efficacy variables included the number of children requiring rescue medication and the time to remedication; the number of children with a body temperature <38 degrees C during the evaluation period and the time to reach this temperature; maximal body temperature reduction; and the weighted sum of changes in body temperature over the evaluation period. Tolerability was assessed based on changes in vital signs, monitored for 6 hours after administration of study drug, and adverse events recorded during the 24 hours after administration. RESULTS: Twenty children received propacetamol and 21 received placebo. Twenty patients were white, 17 black, and 4 Hispanic; their age ranged from 3 to 12 years. The actual mean (SD) dose of propacetamol received was 25.5 (0.6) mg/kg (equivalent to acetaminophen 12.8 [0.3] mg/kg). The reduction in body temperature was significantly greater in the propacetamol group compared with the placebo group at each time point over the 6-hour follow-up period (P < 0.001). Rescue medication was administered to 10.0% of patients in the propacetamol group, compared with 52.4% of those in the placebo group (P = 0.004). The weighted mean (SD) sum of the change in body temperature indicated greater antipyretic efficacy for propacetamol compared with placebo (-7.9 [3.8] degrees C x h vs 0.1 [3.6] degrees C x h, respectively; P < 0.001). There was no difference in the number of patients with treatment-emergent adverse events in the propacetamol and placebo groups (8 [40.0%] and 8 [38.1%]). The incidence of IV-site reactions was 10.0% in the propacetamol group and 9.5% in the placebo group. CONCLUSIONS: In these 41 children with acute fever of infectious origin, a propacetamol dose of 25.5 (0.6) mg/kg IV had significantly greater antipyretic efficacy than placebo and was equally well tolerated. Comparisons of this preparation with other IV antipyretic medications are needed. [ABSTRACT FROM AUTHOR]

Unlabelled: The current management of vesicoureteral reflux (VUR) focuses on the prevention of urinary tract infections (UTI), with curative surgery being limited to those children that fail conservative measures. This is based on the assumption that UTIs are preventable with the use of prophylatic antibiotics, leading to reduction of renal scarring, and the possibility that VUR in children can resolve spontaneously., Methods: Review of the recent literature has demonstrated a growing concern that antibiotic prophylaxis may not lead to prevention of UTIs. Additionally, data indicate that renal scarring may not be preventable with antibiotic prophylaxis or even surgical correction of VUR. An overview of all of the current controversies is presented in this paper., Results: Does antibiotic prophylaxis lead to reduction in UTIs in children with VUR? To address this question, the National Institutes of Health have developed a randomized placebo-controlled study of children with VUR (the RIVUR Study), identified following the development of a UTI., Conclusions: There are far reaching consequences of the results of the RIVUR Study. If antibiotic prophylaxis does not prevent UTI in children with VUR, or lead to reduction in renal scarring, does identification of VUR provide any benefits? Perhaps appropriate treatment of UTI may be all that is necessary for preserving renal function. Final answers will have to wait until the completion of this study.

Pediatricians have an important role to play in the advancement of child health research and should be encouraged and supported to pursue research activities. Education and training in child health research should be part of every level of pediatric training. Continuing education and access to research advisors should be available to practitioners and academic faculty. Recommendations to promote additional research education and support at all levels of pediatric training, from premedical to continuing medical education, as well as suggestions for means to increase support and mentorship for research activities, are outlined in this statement.

Most reports on the effectiveness and side effects of oral versus parenteral calcitriol or alfacalcidol in hemodialysis patients with secondary hyperparathyroidism show no advantage of parenteral treatment. The efficacy and safety of intravenous doxercalciferol (1alphaD(2)) were studied in hemodialysis patients with secondary hyperparathyroidism (plasma intact parathyroid hormone [iPTH]: range, 266 to 3,644 pg/mL; median, 707 pg/mL). These results were compared with those of a previous trial using intermittent oral 1alphaD(2); the same 70 patients were entered onto both trials, and 64 patients completed both trials per protocol. Twelve weeks of open-label treatment in both trials were preceded by identical 8-week washout periods. Degrees of iPTH suppression from baseline were similar in the two trials, with iPTH level reductions less than 50% in 89% and 78% of patients during oral and intravenous treatment, respectively. Grouping patients according to entry iPTH levels (<750 and >/=750 pg/mL) showed similar but more rapid iPTH suppression in the low-iPTH groups, whereas longer treatment and larger doses were required by the high-iPTH groups. Highest serum calcium levels averaged 9.82 +/- 0.14 and 9.67 +/- 0.11 mg/dL during oral and intravenous 1alphaD(2) treatment, respectively (P: = not significant [NS]). Prevalences of serum calcium levels greater than 11.2 mg/dL during oral and intravenous treatment were 3.62% and 0.86% of calcium measurements, respectively (P: < 0.001). Highest serum phosphorus levels during oral and intravenous treatment averaged 5.82 +/- 0.21 and 5.60 +/- 0.21 mg/dL, respectively (P: = NS). The percentage of increments in serum phosphorus levels during oral treatment exceeded that during intravenous treatment during 5 of 12 treatment weeks. Thus, intermittent oral and intravenous therapy with 1alphaD(2) reduced iPTH levels effectively and similarly, hypercalcemia was less frequent, and serum phosphorus levels increased less during intravenous than oral 1alphaD(2) therapy, suggesting that intravenous 1alphaD(2) therapy may be advantageous in patients prone to hypercalcemia or hyperphosphatemia.

Hypercalcemia and hyperphosphatemia frequently necessitate vitamin D withdrawal in hemodialysis patients with secondary hyperparathyroidism. In short-term trials, doxercalciferol (1alpha-hydroxyvitamin D(2) [1alphaD(2)]) suppressed intact parathyroid hormone (iPTH) effectively with minimal increases in serum calcium and phosphorus (P) levels. This modified, double-blinded, controlled trial examined the efficacy and safety of 1alphaD(2) use in 138 hemodialysis patients with moderate to severe secondary hyperparathyroidism by using novel dose titration; 99 patients completed the study. Hemodialysis patients with secondary hyperparathyroidism were enrolled onto this study, consisting of washout (8 weeks), open-label 1alphaD(2) treatment (16 weeks), and randomized, double-blinded treatment with 1alphaD(2) or placebo (8 weeks). Oral 1alphaD(2) was administered at each hemodialysis session, with doses titrated to achieve target iPTH levels of 150 to 300 pg/mL. Baseline iPTH levels (897 +/- 52 [SE] pg/mL) decreased by 20% +/- 3.4% by week 1 (P: < 0.001) and by 55% +/- 2.9% at week 16; iPTH levels returned to baseline during placebo treatment but remained suppressed with 1alphaD(2) treatment. In 80% of the patients, iPTH level decreased by 70%, reaching the target level in 83% of the patients. Grouping patients by entry iPTH level (<600, 600 to 1,200, and >1,200 pg/mL) showed rapid iPTH suppression in the group with the lowest level; greater doses and longer treatment were required in the group with the highest level. During open-label treatment, serum calcium and P levels were 9.2 +/- 0.84 (SD) to 9.7 +/- 1.05 mg/dL and 5.4 +/- 1.10 to 5.9 +/- 1.55 mg/dL, respectively. During double-blinded treatment, serum calcium levels were slightly greater with 1alphaD(2) than placebo, but P levels did not differ. During double-blinded treatment, 3.26% and 0.46% of serum calcium measurements exceeded 11.2 mg/dL with 1alphaD(2) and placebo, respectively (P: < 0.01); median level was 11.6 mg/dL during hypercalcemia. Intermittent oral 1alphaD(2) therapy effectively suppresses iPTH in hemodialysis patients with secondary hyperparathyroidism, with acceptable mild hypercalcemia and hyperphosphatemia.

Three patients with hemolytic uremic syndrome (HUS) developed peripheral gangrene. Bilateral carotid artery thromboses occurred in one of these patients after recovery from HUS. One patient had a long history of juvenile rheumatoid arthritis. In the second patient, a flu-like illness preceded the onset of HUS. The third was one of two sisters, with the HUS appearing more than 1 year apart. None had evidence of disseminated intravascular coagulation or infection with Streptococcus pneumoniae. The patient with rheumatoid arthritis had renal cortical necrosis but recovered moderate renal function after treatment with dialysis and plasmapheresis for 6 months. The child with a genetic form of HUS died of renal failure and had massive cortical necrosis and vascular thrombosis at autopsy. This is the first report of peripheral gangrene in children with idiopathic HUS and autosomal recessive HUS.

Previous studies have shown that the Madin-Darby canine kidney cell taurine transporter (pNCT) is downregulated by protein kinase C (PKC) activation. In this study, it is hypothesized that the highly conserved serine-322 (Ser-322) located in the fourth intracellular segment (S4) may play an important role in the function of taurine transporter, which is modulated by PKC phosphorylation. It is demonstrated that Ser-322 is the critical site of PKC phosphorylation, as determined by site-directed mutagenesis. When Ser-322 of pNCT was changed to alanine (S322A) and this mutant was evaluated in an oocyte expression system, taurine transport activity increased threefold compared with control (wild-type pNCT). Activation of PKC by the active phorbol ester 12-myristate 13-acetate did not influence taurine transport by mutant S322A. Kinetic analysis showed that the mutation of Ser-322 essentially changed the Vmax, rather than the Km, of the transporter. Mutation of all other PKC consensus sites did not affect transporter activity when expressed in the oocyte system. Western blot analysis showed that expression of taurine transporter protein was similar in oocytes injected with either wild-type or mutant pNCT cRNA, indicating that the enhanced taurine transport activity by mutant S322A was not caused by a greater amount of transporter expressed in the oocyte. Furthermore, this study demonstrated that the taurine transporter was phosphorylated after PKC activation, and this effect was not observed in mutant S322A. In conclusion, Ser-322 is critical in PKC regulation of taurine transporter activity. The steady-state taurine transporter activity is tightly controlled by endogenous PKC phosphorylation of Ser-322, which is located in the fourth intracellular segment of the taurine transporter.

Changes in market-driven health care economics are rapid and of great magnitude. This report describes a study of some of these changes in regard to children's health issues. We used a survey tool to assess long-range plans (next 10 years) and marketing strategies for major free-standing children's hospitals in different regions of the United States. We then used these assessments to draw conclusions about the impact of the plans and strategies on the practice of pediatric physicians and their workforce requirements. This may allow pediatric specialists and their programs to develop strategic plans and to take actions to contend with these market-driven economic changes. The tool was a questionnaire mailed to chief executive officers of 30 randomly chosen but geographically well-distributed children's hospitals. Seventeen children's hospitals responded (57%), providing information concerning each hospital and its current medical economic environment. The data were analyzed and trends were then identified from their responses. All institutions in this study expected to have fewer physicians on staff in the future. These institutions plan: (1) to improve quality and (2) to reduce costs. Quality will be improved by utilizing Continuous Quality Improvement (CQI) and/or Benchmarking to Best Practices, both of which encourage physicians to follow standardized treatment protocols. Costs will be reduced by decreasing hospital staff size. Some children's hospitals have merged or will merge with larger, full-service adult hospitals, but most plan to remain autonomous. Many expect a continued decrease in revenues, and almost all expect to downsize both bed number and staff. Restructuring will reduce the number of specialists, particularly in the fields of hematology-oncology, psychiatry, endocrinology, nephrology, and cardiology, and will also reduce the number of surgical specialists. The administrators predicted that more nurse practitioners will be employed at these hospitals in the 21st century, serving the role of physician extenders, if not physician substitutes. To ensure their own survival, physicians must develop their own strategic plans as have the hospitals in which they practice. Optimally they should embrace those activities that parallel their hospital's efforts such as Quality Improvement (CQI, Benchmarking), cost containment, and practice mergers.