Keys to Class II correction: A comparison of 2 extraction protocols.

INTRODUCTION: The purpose of this study was to evaluate the effects of 2 extraction patterns on incisor and molar movements in patients with growing Class II Division 1. METHODS: The sample included 54 patients 10-17 years of age treated by 2 private practice orthodontists using Tweed directional force mechanics, 4 premolar extractions, J-hook headgears, and Class II elastics or Saif springs. The sample was divided on the basis of having maxillary and mandibular first premolars (4/4) or maxillary first and mandibular second premolars (4/5) extracted. Each group included 27 patients. Treatment lasted 2.8 ± 0.60 years and 2.6 ± 0.54 years for the 4/4 and 4/5 groups, respectively. Pretreatment (T1) and posttreatment lateral cephalograms and dental casts were evaluated. Cranial base, mandibular, and maxillary superimpositions were performed to quantify tooth movements and displacements. RESULTS: There were no statistically significant T1 between-group differences in crowding or in the SNA, SNB, ANB, and MPA angles. Analyses of covariance, controlling for statistically significant (P <0.05) differences in T1 mandibular incisor position, showed that mandibular first premolars extractions produced greater (1.6 mm) mandibular incisor retraction than second premolar extractions. The mandibular first molars were protracted significantly more (0.7 mm) after the second premolar than the first premolar extractions. Within-group changes of the MPA, between-group differences in the changes in MPA, and the amount of vertical eruption of the maxillary and mandibular molars were not significantly different between the 2 extraction patterns. CONCLUSIONS: Extraction of mandibular second premolars enhances Class II molar correction, with greater mesial first molar movement and less distal incisor movement. Neither extraction pattern has an effect on the MPA or the vertical dimension (ie, there was no "wedge effect").

The first-in-human study of the hydrogen sulfate (Hyd-sulfate) capsule of the MEK1/2 inhibitor AZD6244 (ARRY-142886): a phase I open-label multicenter trial in patients with advanced cancer.

PURPOSE: In part A, the aim was to define the maximum tolerated dose (MTD) of the hydrogen sulfate (Hyd-Sulfate) oral capsule formulation of the mitogen-activated protein kinase kinase inhibitor AZD6244 (ARRY-142886). In part B, the aim was to compare the pharmacokinetic profile of the new Hyd-Sulfate capsule with the initial AZD6244 free-base suspension and further characterize the pharmacodynamic profile and efficacy of the new formulation. EXPERIMENTAL DESIGN: In part A, 30 patients received escalating doses of AZD6244 Hyd-Sulfate twice daily. In part B, 29 patients were randomized to a single dose of the Hyd-Sulfate capsule or free-base suspension, followed by a washout, then a single dose of the alternative formulation. Patients received the Hyd-Sulfate capsule twice daily at MTD of part A thereafter. RESULTS: The MTD of the Hyd-Sulfate capsule was 75 mg twice daily. Dose limiting toxicities were Common Terminology Criteria for Adverse Events grade 3 acneiform rash and pleural effusion. Fatigue (65.7%) and acneiform dermatitis (60.0%) were the most frequent adverse events at the MTD. Based on area under curve(0-24), exposure of the 75 mg Hyd-Sulfate capsule relative to the 100 mg free-base suspension was 197% (90% confidence interval, 161-242%). Pharmacodynamic analysis showed that inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced extracellular signal-regulated kinase phosphorylation in peripheral blood lymphocytes was related to plasma concentrations of AZD6244, with an estimated IC(50) of 352 ng/mL and maximum inhibition (E(max)) of approximately 91%, showing target inhibition. A patient with metastatic melanoma bearing a V600E BRAF mutation achieved a complete response persisting after 15 months of therapy. CONCLUSIONS: The AZD6244 Hyd-Sulfate capsule formulation has shown a favorable toxicity, pharmacokinetic, and pharmacodynamic profile, and is being taken forward in ongoing clinical trials.

The pathological expressions of Brunners gland hyperplasia into adenoma and hamartoma.

The terms Brunners gland adenoma and hamartoma are 2 pathological expressions of hyperplasia of these glands. We report 3 patients and review the recent literature to support our hypothesis of common pathology. Awareness of the existence and character of Brunners gland lesions will increase the possibility of their accurate diagnosis.