Faculty Bibliography

The present experiment investigated the developmental aspects of source compared to item memory. College students and 7-8-year-old children viewed pictures drawn in red or green during a study phase, and were asked either to remember the pictures for a subsequent recognition test, or to remember both the pictures and their associated colors for a subsequent source memory test. In the test phase, new and old pictures were presented in black. In the recognition task, participants were asked to make binary old/new recognition judgments, while in the source task, they were asked to make trinary old-green/old-red/new source judgements. Performance on all tasks improved with increasing age, but the age difference for source was much larger than that for item memory. It has been suggested that the frontal lobes play a critical role in the retrieval of source information, and that this brain region relative to the medial temporal lobes continues to develop into late adolescence. Thus, it is possible that immaturity of the frontal lobes may be causally related to the children's lower performance on the source memory task.

OBJECTIVE: Electrocardiographic repolarization intervals were evaluated to determine the extent of cardiac autonomic dysfunction in patients with familial dysautonomia (FD) and to determine if any of these intervals could serve as a possible predictor of clinical symptoms. METHODS: Thirty-seven electrocardiograms of patients with FD were retrospectively evaluated. QT, JT, rate-corrected QT and JT intervals were calculated as well as QT and QTC dispersion. Results were compared to normative data and electrocardiograms of 20 age-matched control subjects. OBSERVATIONS: In the FD group, prolongation of QTC (>450 msec) was noted in 5/37 (13.5%) patients, as compared to 0/20 normal controls (p = NS), and prolongation of JTc (>340 msec) in 16/37 (43.3%) patients, as compared to 0/20 normal controls (p < 0.001). QT and QTC dispersion were abnormal in 3/37 (8.1%) and 5/37 (13.5%), respectively. In the 16 FD patients with prolonged JTc, six had a positive history of syncope, whereas none of the 21 with normal JTc had syncope or symptoms suggesting arrhythmia (p < 0.003). The positive predictive value of having syncope or symptoms suggestive of arrhythmia with an abnormal JTc is 37.5% (95% CI [15%, 65%]). The negative predictive value is 100% (95% CI [87%, 100%]). CONCLUSION: In the FD population, the electrocardiographic measure of repolarization that was most frequently abnormal was the JTc interval . Prolongation of the JTc interval was significantly more frequent than prolongation of the QTC interval (p < 0.001) QT and QTC dispersions were less significantly affected in the FD population, indicating uniform ventricular recovery time. These results suggest that a prolonged JTc interval may be a more sensitive indicator of abnormal ventricular repolarization and cardiac autonomic dysfunction. Due to the known sympathetic denervation inherent in patients with FD, they are at risk for unopposed parasympathetic predominance. FD patients, therefore, are more likely to have brady arrhythmias and asystole rather than polymorphic ventricular tachycardia. The increased incidence of syncope in patients with prolonged JTc suggests that this measure may serve as a helpful marker to predict which FD patients are at increased risk of serious clinical sequelae including bradyarrhythmias with asystole or sudden death

BACKGROUND: Fluconazole has proven to be safe and effective for a variety of superficial and systemic fungal infections. Preliminary analysis of extensive Phase III studies suggests that it is very effective for the treatment of onychomycosis. Its pharmacokinetic properties, including low molecular weight and high water-solubility, suggest a unique ability to penetrate the nail. This feature is likely to account in part for fluconazole's effectiveness in the treatment of onychomycosis. OBJECTIVE: Determinations of plasma and fingernail concentrations of fluconazole were performed as part of a larger study comparing the safety and efficacy of once-weekly fluconazole (150, 300, and 450 mg) to placebo in the treatment of distal subungual onychomycosis of the fingernails caused by dermatophytes. The relationship between fluconazole concentrations and efficacy was also examined. METHODS: Pharmacokinetic studies were performed by means of plasma and fingernail samples from 133 patients, a subset of 349 patients participating in a double-blind, placebo-controlled clinical trial of fluconazole administered in once-weekly doses of 150, 300, or 450 mg until cure of onychomycosis or for a maximum of 9 months. Blood and fingernail samples for pharmacokinetic analysis were taken at baseline, at week 2, and at monthly intervals during the treatment phase of the study. Patients considered clinically cured or improved also participated in a 6-month follow-up study. During this phase, patients were monitored and samples taken every 2 months. RESULTS: Significant amounts of fluconazole were detected in the earliest fingernail samples taken (after 2 weeks of treatment). After two weekly doses, 30% to 33% of steady-state concentrations had been achieved in healthy nails and 22% to 29% in affected nails. Steady state was achieved in 3 to 5 months. Fluconazole concentration in nails as well as plasma followed dose-proportional pharmacokinetics. Nail:plasma ratios in affected nails were 0.4 to 0.6 at 2 weeks and 1.7 to 1.8 at 6 months. Fluconazole concentrations fell slowly after drug discontinuation and were still detectable 4 months after end of treatment. A statistically significant correlation was found between steady-state concentration and clinical and global outcomes. CONCLUSION: Fluconazole rapidly penetrates the fingernail, where it is retained at detectable levels for at least 4 months after drug discontinuation. A significant correlation exists between fluconazole concentration in the fingernails and clinical and global outcomes