Dissolving Potassium Tablets Masquerading as Concealed Foreign Body Ingestion.

Foreign body ingestion is a common consultation for gastroenterologists. Without knowing the object(s) ingested, the differential diagnosis is broad, especially in patients with underlying mental health conditions, such as uncontrolled bipolar disorder, prior suicide attempts, or recreational drug use. The differential should include substances taken with suicidal intent or for concealment of illicit drugs. Certain foreign objects may require urgent or emergent endoscopic intervention. However, one should also consider benign, iatrogenic causes such as large, radiolucent potassium pills given in the emergency department, which do not require further intervention or hospitalization.

The facile and visualizable identification of broad-spectrum inhibitors of MDM2/p53 using co-expressed protein complexes.

MDM2 is a well-known oncoprotein overexpressed in a variety of cancers, and the identification of inhibitors that disrupt the MDM2/p53 interaction is of great interest in anticancer drug development. Here we designed a platform for the facile and visualizable identification of inhibitors of MDM2 using co-expressed protein complexes of MDM2/p53. A hexahistidine-tag on MDM2 allows the binding of the protein complex to the Ni-NTA affinity resin, while the fluorescent protein fused to p53 enables the direct visualization of the interaction of p53 with MDM2. Hence, the inhibition of the MDM2/p53 interaction can be observed with the naked eye. The assay can be set up by directly loading cell lysate to the Ni-NTA affinity resin, and no chemical modification of proteins is needed. In addition to the qualitative analyses, the binding affinity of inhibitors to the MDM2 protein can be quantified by fluorescence titration. The applications of this system have been verified using small molecules and peptide inhibitors. As a proof of concept, we screened a small library using this platform. Interestingly, two types of novel inhibitors of MDM2, including cyclohexyl-triphenylamine derivatives and platinum complexes, were identified and their binding affinities were obtained. Quantitative measurements show that these new types of inhibitors demonstrate a high binding affinity (up to Kd = 51.9 nM) to MDM2.

Metal-free supercapacitor with aqueous electrolyte and low-cost carbon materials.

Electric double-layer capacitors (EDLCs) or supercapacitors (SCs) are fast energy storage devices with high pulse efficiency and superior cyclability, which makes them useful in various applications including electronics, vehicles and grids. Aqueous SCs are considered to be more environmentally friendly than those based on organic electrolytes. Because of the corrosive nature of the aqueous environment, however, expensive electrochemically stable materials are needed for the current collectors and electrodes in aqueous SCs. This results in high costs for a given energy-storage capacity. To address this, we developed a novel low-cost aqueous SC using graphite foil as the current collector and a mix of graphene, nanographite, simple water-purification carbons and nanocellulose as electrodes. The electrodes were coated directly onto the graphite foil by using casting frames and the SCs were assembled in a pouch cell design. With this approach, we achieved a material cost reduction of greater than 90% while maintaining approximately one-half of the specific capacitance of a commercial unit, thus demonstrating that the proposed SC can be an environmentally friendly, low-cost alternative to conventional SCs.

Single-dose pharmacokinetics and safety of azilsartan medoxomil in children and adolescents with hypertension as compared to healthy adults.

PURPOSE: This open-label, multicenter, single-dose study characterized the pharmacokinetics and short-term safety of azilsartan medoxomil (AZL-M) in hypertensive pediatric subjects (12-16 years [cohort 1a; n = 9]; 6-11 years [cohort 2; n = 8]; 4-5 years [cohort 3; n = 3]). METHODS: Model-based simulations were performed to guide dosing, especially in 1-5-year olds, who were difficult to enroll. AZL-M was dosed according to body weight (20-60-mg tablet, cohorts 1a and 2; 0.66 mg/kg granule suspension, cohort 3). In cohort 1, gender-matched healthy adults (cohort 1b; n = 9) received AZL-M 80 mg. RESULTS: Exposure to AZL (active moiety of AZL-M), measured by dose-/body weight-normalized C max and AUC0-∞, was ∼15-30 % lower in pediatric subjects versus adults. In simulations, exposure with 0.66 mg/kg AZL-M in pediatric subjects weighing 8-25 kg approximated to AZL-M 40 mg (typical starting dose) in adults. The simulations suggest that 25-50-kg subjects require half the adult dose (10-40 mg), whereas 50-100-kg subjects can use the same dosing as adults. Adverse events were mild in intensity, apart from one moderate event (migraine). CONCLUSIONS: This dosing strategy should be safe in pediatric patients, as AZL exposure would not exceed that seen in adults with the highest approved AZL-M dose (80 mg).

Acute and longer-term safety results from a pooled analysis of duloxetine studies for the treatment of children and adolescents with major depressive disorder.

OBJECTIVE: To assess acute and longer-term safety of duloxetine in the treatment of children and adolescents with major depressive disorder (MDD), a pooled analysis of data from two completed randomized, double-blind, multicenter, phase 3, placebo- and active-controlled trials was undertaken. In these studies, neither duloxetine (investigational drug) nor fluoxetine (active control) demonstrated a statistically significant improvement compared with placebo on the primary efficacy measure. METHODS: Patients ages 7-17 years with MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) received duloxetine (n=341), fluoxetine (n=234), or placebo (n=225) for 10 week acute and 26 week extended (duloxetine or fluoxetine only) treatments. Safety measures included treatment-emergent adverse events (TEAEs), the Columbia-Suicide Severity Rating Scale, vital signs, electrocardiograms, laboratory samples, and growth (height and weight) assessments. RESULTS: Significantly more patients discontinued because of adverse events during duloxetine (8.2%) treatment than during placebo (3.1%) treatment (p≤0.05). TEAEs in >10% of duloxetine-treated patients were headache and nausea. No completed suicides or deaths occurred. During acute treatment, 6.6% of duloxetine-, 8.0% of fluoxetine-, and 8.2% of placebo-treated patients had worsening suicidal ideation from baseline. Among patients initially randomized to duloxetine or fluoxetine who had suicidal ideation at study baseline, 81% of duloxetine- and 77% of fluoxetine-treated patients had improvements in suicidal ideation at end-point in the 36-week studies. Suicidal behavior occurred in two fluoxetine-treated patients and one placebo-treated patient during acute treatment, and in seven duloxetine-treated patients and one fluoxetine-treated patient during extended treatment. Duloxetine-treated patients had a mean pulse increase of ∼3 beats per minute, and mean blood pressure (both systolic and diastolic) increases of <2.0 mm Hg at week 36. Weight decrease (≥3.5%) during acute treatment occurred with statistically (p≤0.05) greater frequency for both the duloxetine (11.4%) and fluoxetine (11.5%) groups versus the placebo (5.5%) group; however, mean weight increase occurred for both duloxetine and fluoxetine groups during extended treatment. CONCLUSION: Results from this pooled analysis of two studies were consistent with the known safety and tolerability profile of duloxetine. Clinical Trial Registry Numbers: NCT00849901 and NCT00849693.

A randomized, open-label, dose-response study of losartan in hypertensive children.

BACKGROUND AND OBJECTIVES: Once-daily losartan reduces BP in a dose-dependent manner and is well tolerated in hypertensive children aged 6-16 years. This study assessed the dose-response relationship, safety, and tolerability of losartan in hypertensive children aged 6 months to 6 years. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a 12-week, randomized, open-label, dose-ranging study, with a 2-year extension. Patients were randomized to losartan at the following dosages: 0.1 mg/kg per day (low), 0.3 mg/kg per day (medium), or 0.7 mg/kg per day (high). Losartan was titrated to the next dose level (to a 1.4 mg/kg per day maximum dosage, not exceeding 100 mg/d, which was not one of the three original doses offered at randomization) at weeks 3, 6, and 9 for patients who did not attain their goal BP and were not taking the highest dose. Dose response was evaluated by analyzing the slope of change in sitting systolic BP (SBP; primary end point) and diastolic BP (DBP; secondary end point) after 3 weeks compared with baseline. Adverse events (AEs) were recorded throughout. RESULTS: Of the 101 patients randomized, 99 were included in the analysis (low dose, n=32; medium dose, n=34; and high dose, n=33). Mean sitting BP decreased from baseline in the low-, medium-, and high-dose groups by 7.3, 7.6, and 6.7 mmHg, respectively, for SBP and 8.2, 5.1, and 6.7 mmHg, respectively, for DBP after 3 weeks. No dose-response relationship was established by the slope analysis on SBP (P=0.75) or DBP (P=0.64). The BP-lowering effect was observed throughout the 2-year extension. The incidence of AEs was low and comparable between groups. CONCLUSIONS: Hypertensive children aged 6 months to 6 years treated with losartan 0.1-0.7 mg/kg per day had clinically significant decreases from baseline in SBP and DBP, yet no dose-response relationship was evident. Losartan, at a dosage up to 1.4 mg/kg per day, was well tolerated.

CLARA: an integrated clinical research administration system.

Administration of human subject research is complex, involving not only the institutional review board but also many other regulatory and compliance entities within a research enterprise. Its efficiency has a direct and substantial impact on the conduct and management of clinical research. In this paper, we report on the Clinical Research Administration (CLARA) platform developed at the University of Arkansas for Medical Sciences. CLARA is a comprehensive web-based system that can streamline research administrative tasks such as submissions, reviews, and approval processes for both investigators and different review committees on a single integrated platform. CLARA not only helps investigators to meet regulatory requirements but also provides tools for managing other clinical research activities including budgeting, contracting, and participant schedule planning.

Losartan and enalapril are comparable in reducing proteinuria in children with Alport syndrome.

BACKGROUND: A previous subgroup analysis of a 12-week, double-blind study demonstrated that losartan significantly lowered proteinuria versus placebo and amlodipine and was well tolerated in children (1-17 years old) with proteinuria secondary to Alport syndrome. The present subgroup analysis of the open-label, extension phase of this study assessed the long-term efficacy and tolerability of losartan versus enalapril. METHODS: Patients who had completed the double-blind study were re-randomized to losartan or enalapril and followed for proteinuria and renal function for up to 3 years. RESULTS: Twenty-seven patients with Alport syndrome were randomized to losartan (0.44-2.23 mg/kg/day; n = 15) or enalapril (0.07-0.72 mg/kg/day; n = 12). The least-squares (LS) mean percent change from week 12 in urinary protein to creatinine ratio (UPr/Cr was +1.1 % in the losartan group versus a further 13.9 % reduction in the enalapril group (GMR [95 % CI] = 1.2 [0.7, 2.0]); the LS mean change from week 12 in estimated glomerular filtration rate (eGFR) was -6.4 ml/min/1.73 m(2) in the losartan group versus -9.1 ml/min/1.73 m(2) in the enalapril group. The adverse event incidence was low and comparable in both treatment groups. CONCLUSIONS: In children with proteinuria secondary to Alport syndrome, losartan maintained proteinuria reduction, and enalapril produced a further proteinuria reduction over the 3-year study period. Both agents were generally well tolerated.

Pharmacokinetics of olmesartan medoxomil in pediatric patients with hypertension.

BACKGROUND: The prevalence and importance of hypertension in younger patients is becoming increasingly recognized; however, only a limited number of clinical trials have been conducted in the pediatric population. OBJECTIVE: The aim of this study was to characterize the pharmacokinetics and short-term safety of olmesartan medoxomil in children and adolescents with hypertension. METHODS: An open-label, multicenter, single-dose study was conducted in children and adolescents aged 12 months-16 years who were receiving treatment for hypertension or, if not currently treated for hypertension, had either a systolic blood pressure (SBP) or diastolic blood pressure (DBP).≥95th percentile, or SBP or DBP ≥90th percentile if diabetic or with a family history of hypertension. Patients were stratified by age: 12-23 months (Group 1; none enrolled), 2-5 years (Group 2; n = 4), 6-12 years (Group 3; n = 10), and 13-16 years (Group 4; n = 10). All patients received a single oral dose of olmesartan medoxomil based on the individual's age and bodyweight. Patients aged <6 years received an oral suspension of olmesartan medoxomil at a dose of 0.3 mg/kg of bodyweight (not to exceed 20 mg), those aged ≥6 years who weighed ≥35 kg received olmesartan medoxomil 40 mg tablets, and those who weighed <35 kg received olmesartan medoxomil 20 mg tablets. RESULTS: In Groups 2, 3, and 4, the weight-adjusted apparent total body clearance (CL/F) of olmesartan medoxomil was 0.100 ± 0.034, 0.062 ± 0.020, and 0.072 ± 0.022 L/h/kg, respectively, and the weight-adjusted apparent volume of distribution (Vd/F) was 0.32 ± 0.16, 0.33 ± 0.14, and 0.49 ± 0.23 L/kg, respectively. CL/F and Vd/F in Groups 3 and 4 were not significantly different. Statistical comparisons between Groups 3 or 4 and Group 2 were not performed due to the small sample size of Group 2 (n = 4). Plasma elimination half-life and time to maximum plasma concentration were similar across the three groups. In Groups 3 and 4, considerable interindividual variability was seen in maximum plasma concentration (C(max)), area under the curve (AUC) from time zero to the last measurable concentration, and apparent clearance, with AUC and C(max) approximately 30% greater in Group 3. Four of 24 (16.7%) patients experienced treatment-emergent adverse events that were all mild in severity and considered not drug-related. No deaths, serious adverse events, or discontinuations due to adverse events occurred in the study. CONCLUSIONS: Olmesartan medoxomil was well tolerated and demonstrated a pharmacokinetic profile in pediatric patients similar to that of adults when adjusted for body size. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00151814

Losartan and enalapril are comparable in reducing proteinuria in children.

Angiotensin-converting enzyme inhibitors and angiotensin II type I receptor blockers delay progression of chronic kidney disease and have antiproteinuric effects beyond their effects on blood pressure. They are routinely used in adults; however, their efficacy and safety in children, in whom the causes of chronic kidney disease are significantly different relative to adults, is uncertain. Here we assessed an open-label extension of a previous 3-month blinded trial, in which the efficacy and tolerability of losartan was compared to placebo or amlodipine in 306 normotensive and hypertensive children with proteinuria. In this study, 268 children were re-randomized to losartan or enalapril and followed until 100 patients completed 3 years of follow-up for proteinuria and renal function. The least squares percent mean reduction from baseline in the urinary protein/creatinine ratio was 30.01% for losartan and 40.45% for enalapril. The least squares mean change from baseline in eGFR was 3.3 ml/min per 1.73 m2 for losartan and 7.0 ml/min per 1.73 m2 for enalapril. The incidence of specific adverse events such as hyperkalemia and renal dysfunction was low and similar in both groups. Both were generally well tolerated and, overall, fewer drug-related adverse events occurred with losartan than with enalapril. Thus, in children with proteinuria, losartan and enalapril significantly reduced proteinuria without any appreciable changes in eGFR, effects that were maintained throughout the study. Both losartan and enalapril were generally well tolerated.

Effect of placebo on ambulatory blood pressure monitoring in children.

BACKGROUND: Ambulatory blood pressure monitoring (ABPM) has been proposed as a useful tool for more accurately diagnosing hypertension (HTN) and evaluating blood pressure (BP) response in pediatric anti-hypertensive trials. ABPM captures multiple BP measurements during routine daily activities and is thus an excellent method for identifying white-coat HTN. Additionally, ABPM measurements in adults do not demonstrate the placebo effect commonly seen with casual BP measurements, although this has yet to be evaluated in children. Therefore,, the aim of this study was to assess the effect of placebo on ABPM measurements in children. METHODS: A total of 141 children aged 5-16 years with elevated BP were randomized into a multi-center, single-blind, cross-over trial. Subjects received a placebo pill prior to wearing a 24-h ABPM device at one of two visits separated by 1-2 weeks. Study procedures were otherwise identical at both visits. RESULTS: Mean systolic and diastolic BP for all measured time periods were similar between visits, as was the number of children diagnosed with HTN at each visit. CONCLUSION: Having confirmed HTN at baseline did not affect the impact of placebo on mean BP. If confirmed, this lack of placebo effect on ABPM measurements may allow for the design of direct comparison pediatric anti-hypertensive trials without a placebo arm.

Effectiveness and safety of valsartan in children aged 6 to 16 years with hypertension.

The effectiveness and safety of valsartan have not been assessed in hypertensive children. Therefore, hypertensive patients aged 6 to 16 years (n=261) were randomized to receive weight-stratified low- (10/20 mg), medium- (40/80 mg), or high-dose (80/160 mg) valsartan for 2 weeks. After 2 weeks, patients were randomized to a 2-week placebo-controlled withdrawal phase. Dose-dependent reductions in sitting systolic blood pressure (SSBP) and sitting diastolic blood pressure (SDBP) were observed after 2 weeks (low dose, -7.9/-4.6 mm Hg; medium dose, -9.6/-5.8 mm Hg; high dose, -11.5/-7.4 mm Hg [P<.0001 for all groups]). During the withdrawal phase, SSBP and SDBP were both lower in the pooled valsartan group than in the pooled placebo group (SSBP, -2.7 mm Hg [P=.0368]; SDBP, -3.0 mm Hg [P=.0047]). Similar efficacy was observed in all subgroups. Valsartan was well tolerated and headache was the most commonly observed adverse event during both the double-blind and 52-week open-label phases.

Efficacy and safety of losartan in children with Alport syndrome--results from a subgroup analysis of a prospective, randomized, placebo- or amlodipine-controlled trial.

BACKGROUND: No prospective, randomized, double-blind trials of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have previously been reported in adults or children with proteinuria secondary to Alport syndrome. METHODS: This 12-week, double-blind multinational study investigated the effects of losartan 0.7-1.4 mg/kg/day compared with placebo (normotensive patients) or amlodipine 0.1-0.2 mg/kg/day up to 5 mg/day (hypertensive patients) on proteinuria [early morning-void urinary protein/creatinine ratio (UPr/Cr), baseline ≥ 34 mg/mmol] in 30 children of up to 17 years of age with Alport syndrome. RESULTS: Twelve weeks of treatment with losartan significantly reduced proteinuria compared with placebo/amlodipine: losartan -14.7 mg/mmol (interquartile range -49.7 to -5.7 mg/mmol) or 31.6% reduction using a mixed model approach versus placebo/amlodipine 2.3 mg/mmol (-26.0 to 18.1 mg/mmol), P = 0.01 or 2.3% increase using a mixed model approach. Adverse event incidence was low and comparable between losartan and placebo/amlodipine groups. CONCLUSIONS: Losartan significantly lowered proteinuria and was well tolerated after 12 weeks of treatment in children aged 1-17 years with proteinuria secondary to Alport syndrome with or without hypertension, a population that has not previously been rigorously studied.

Safety, efficacy, and pharmacokinetics of telmisartan in pediatric patients with hypertension.

OBJECTIVE: To assess the safety, pharmacokinetics (PKs), and blood pressure (BP)-lowering efficacy of telmisartan in pediatric (6 to <18 years) patients with hypertension. STUDY DESIGN: Patients with diagnosed hypertension were randomized to 4 weeks of treatment with placebo, or with 1 of 2 nominal telmisartan dose levels (1 mg/kg/d or 2 mg/kg/d). The primary end point was change in seated systolic BP (SBP) from baseline to study end. RESULTS: A total of 77 patients were randomized and received at least 1 dose of study medication (placebo, n = 16; low-dose telmisartan, n = 30; high-dose telmisartan, n = 31). Adjusted mean changes (standard errors) in SBP from baseline to study end were -6 (2.4), -14 (1.7), and -9.7 (1.7) mm Hg, respectively, in the placebo, high-dose telmisartan, and low-dose telmisartan groups. CONCLUSIONS: Telmisartan may be an appropriate therapy for treatment of pediatric hypertension, although more extensive studies are required in patients younger than age 12.

Arabinogalactan protein from Jatropha curcas L. seeds as TGFß1-mediated inductor of keratinocyte in vitro differentiation and stimulation of GM-CSF, HGF, KGF and in organotypic skin equivalents.

Arabinogalactan protein JC from Jatropha curcas seed endosperm (mean molecular weight 140 kDa) was isolated by cold water extraction and characterized concerning sugar and amino acid composition. At 10 and 100 µg/mL JC stimulated mitochondrial activity (MTT test) of human skin cells (HaCaT keratinocytes, fibroblasts) and the ATP status of primary keratinocytes. JC did not influence the cellular proliferation, while primary keratinocytes were triggered into differentiation status. Investigations on a potential mode of action of JC were performed on complex organotypic skin equivalents. JC induced the production of HGF, KGF and TGFß, with TGFß being the main inductor for the differentiation-inducing effect of JC. Also the expression of GM-CSF was stimulated strongly by JC. This in vitro activity profile indicated JC to be a potent inductor of cellular differentiation via stimulation of growth hormones and TGF-ß-induced cell signaling.

Randomized, double-blind, controlled study of losartan in children with proteinuria.

BACKGROUND AND OBJECTIVES: No large, randomized, double-blind trials in children with proteinuria treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have previously been reported. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This 12-week, double-blind, multinational study investigated the effects of losartan 0.7 to 1.4 mg/kg per day compared with placebo (normotensive stratum) or amlodipine 0.1 to 0.2 mg/kg per day up to 5 mg/d (hypertensive stratum) on proteinuria (morning-void urinary protein-creatinine ratio, baseline > or =0.3 g/g) in 306 children up to 17 years of age. RESULTS: Twelve weeks of treatment with losartan significantly reduced proteinuria compared with amlodipine/placebo: losartan -35.8% (95% confidence interval: -27.6% to -43.1%) versus amlodipine/placebo 1.4% (95% confidence interval: -10.3% to 14.5%), P < or = 0.001. Significance remained after adjustment for differences across treatment groups in change in BP (losartan produced incremental systolic and diastolic BP reductions versus amlodipine of 5.4 and 4.6 mmHg, respectively; and versus placebo of 3.8 and 4.0 mmHg, respectively). Proteinuria reduction was consistently observed in the normotensive (-34.4% losartan; 2.6% placebo) and hypertensive (-41.5% losartan; 2.4% amlodipine) strata, and in all prespecified subgroups, including age, gender, race, Tanner stage, weight, prior therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, as well as among the most common etiologies of proteinuria. Adverse event incidence was low and comparable in all groups. CONCLUSIONS: Losartan significantly lowered proteinuria and was well tolerated after 12 weeks in children aged 1 to 17 years with proteinuria with or without hypertension, a population that has not previously been rigorously studied.

Pharmacokinetics of valsartan in pediatric and adolescent subjects with hypertension.

An open-label, single-dose study is conducted in 26 children with hypertension to characterize the pharmacokinetics of valsartan. Valsartan is administered as an oral suspension (dose of 2 mg/kg), with the maximum single dose being 80 mg. Subjects are stratified into 4 age categories: group 1, 1 to less than 4 years; group 2, 4 to less than 6 years; group 3, 6 to less than 12 years; group 4, 12 to 16 years. Blood samples are collected before and for 24 hours after dosing to quantitate valsartan. Because the body weight of most children in groups 3 and 4 exceeds 40 kg and they received a dose of less than 2 mg/kg, major pharmacokinetic parameters are dose normalized for comparison across the age groups. Dose-normalized maximum plasma concentration and area under the plasma-concentration curve and body weight-normalized apparent oral clearance are comparable for the 4 groups (P > or = .1011). Body weight-normalized apparent oral clearance ranges from 0.061 to 0.089 L/h/kg.

Candesartan cilexetil effectively reduces blood pressure in hypertensive children.

BACKGROUND: The angiotensin-receptor blocker candesartan cilexetil is a well-tolerated antihypertensive agent with demonstrated benefits in adults with hypertension. However, there are few data supporting its use in children with hypertension. OBJECTIVE: To determine the efficacy and tolerability of candesartan cilexetil in the treatment of pediatric hypertension. METHODS: In an open-label, uncontrolled pilot study, hypertensive pediatric patients were eligible for participation if untreated systolic and/or diastolic blood pressure (BP) exceeded the 95th percentile for sex, age, and height. Patients underwent a 7-day washout period prior to initiation of weight-based dosing of candesartan cilexetil (2-8 mg daily). The dose was doubled after 7 days of therapy if inadequate antihypertensive response was determined by clinic-measured casual BP monitoring (CBPM) and home BP monitoring (HBPM). Three methods of BP measurement were compared before and after 2 weeks of treatment with the final dose of candesartan cilexetil: CBPM, HBPM, and 24-hour continuous ambulatory BP monitoring (ABPM). Self-reported adverse effects and clinical laboratory analyses were used to determine tolerability. RESULTS: Eleven patients (mean age 14.2 y) received a final candesartan cilexetil median daily dose of 8 mg (0.13 mg/kg, range 2-16 mg). Study treatment resulted in significant reductions in systolic and diastolic BP as measured by CBPM (-7.4%, p = 0.03 and -5.9%, p = 0.01, respectively) and by ABPM (-6.0%, p = 0.03 and -10.8%, p = 0.006, respectively), but no significant reductions as measured by HBPM. No clinically significant changes in laboratory measures were observed, and patients reported nonspecific mild adverse effects. CONCLUSIONS: Candesartan cilexetil effectively reduced BP as demonstrated by CBPM and ABPM measurements and was well tolerated in this group of hypertensive children.