Mineral trioxyde aggregate versus calcium hydroxide in apexification of non vital immature teeth: study protocol for a randomized controlled trial.

BACKGROUND: Pulp necrosis is one of the main complications of dental trauma. When it happens on an immature tooth, pulp necrosis implies a lack of root maturation and apical closure. A therapy called apexification is required to induce the formation of a calcified apical barrier allowing a permanent and hermetic root filling. The aim of this prospective randomized clinical trial is to compare Mineral Trioxide Aggregate(MTA)with Calcium Hydroxide(CH)as materials used to induce root-end closure in necrotic permanent immature incisors. METHODS/DESIGN: This study, promoted by AP-HP, was approved by the ethics committee(CPP Paris Ile de France IV). 34 children aged from 6 to 18 years and presenting a non-vital permanent incisor are selected. Prior to treatment, an appropriate written consent has to be obtained from both parents and from children. Patients are then randomly assigned to either the MTA(experimental)or CH(control)groups. Recalls are performed after 3, 6 and 12 months to determine the presence or absence of a calcified apical barrier through the use of clinical and radiographic exams. Additional criteria such as clinical symptoms, apical radiolucencies, periapical index(PAI)are also noted. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT00472173 (First inclusion: May 10, 2007; Last inclusion: April 23, 2009; study completed: April 15, 2010).

Bacteriuria in a geriatric hospital: impact of an antibiotic improvement program.

OBJECTIVES: To prospectively evaluate a management approach to bacteriuria including advice from an infectious diseases consultant (IDC) in geriatric inpatients. DESIGN: Prospective study from July 1, 2003, to June 30, 2004. SETTING: A 205-bed geriatric university-affiliated hospital. PARTICIPANTS: Consecutive hospitalized patients with positive urine cultures. INTERVENTION: The hospital's infection control department developed recommendations about antimicrobial use for bacteriuria, which were discussed at staff meetings. Treatments for bacteriuria prescribed by ward physicians were reviewed by an IDC, who suggested changes where appropriate. Physicians were free to follow or to disregard the IDC's suggestions. MEASUREMENTS: Patients with positive urine cultures (UC) were classified as having asymptomatic bacteriuria (AB), urinary tract infection (UTI) or pyelonephritis (PN). Prescribed and actual treatments were compared. RESULTS: Of 252 consecutive positive UCs in 181 patients, 124 (49%) were classified as AB, 88 (35%) as UTI, and 38 (15%) as PN; 2 cases of prostatitis were excluded. The total number of prescribed antimicrobial days before IDC advice was 729 and the actual number (after IDC advice) was 577, for a 152-day (21%) reduction. Most of the reduction was generated by shortening the treatment duration. CONCLUSION: Intervention of an IDC resulted in reduced antimicrobial use in older inpatients with bacteriuria.

In vitro metabolism of chloroquine: identification of CYP2C8, CYP3A4, and CYP2D6 as the main isoforms catalyzing N-desethylchloroquine formation.

In humans, the antimalarial drug chloroquine (CQ) is metabolized into one major metabolite, N-desethylchloroquine (DCQ). Using human liver microsomes (HLM) and recombinant human cytochrome P450 (P450), we performed studies to identify the P450 isoform(s) involved in the N-desethylation of CQ. In HLM incubated with CQ, only DCQ could be detected. Apparent Km and Vmax values (mean +/- S.D.) for metabolite formation were 444 +/- 121 microM and 617 +/- 128 pmol/min/mg protein, respectively. In microsomes from a panel of 16 human livers phenotyped for 10 different P450 isoforms, DCQ formation was highly correlated with testosterone 6beta-hydroxylation (r = 0.80; p < 0.001), a CYP3A-mediated reaction, and CYP2C8-mediated paclitaxel alpha-hydroxylation (r = 0.82; p < 0.001). CQ N-desethylation was diminished when coincubated with quercetin (20-40% inhibition), ketoconazole, or troleandomycin (20-30% inhibition) and was strongly inhibited (80% inhibition) by a combination of ketoconazole and quercetin, which further corroborates the contribution of CYP2C8 and CYP3As. Of 10 cDNA-expressed human P450s examined, only CYP1A1, CYP2D6, CYP3A4, and CYP2C8 produced DCQ. CYP2C8 and CYP3A4 constituted low-affinity/high-capacity systems, whereas CYP2D6 was associated with higher affinity but a significantly lower capacity. This property may explain the ability of CQ to inhibit CYP2D6-mediated metabolism in vitro and in vivo. At therapeutically relevant concentrations ( approximately 100 microM CQ in the liver), CYP2C8, CYP3A4, and, to a much lesser extent, CYP2D6 are expected to account for most of the CQ N-desethylation.