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Biomedical subjects

David Wexler

Publications and source records attributed to David Wexler.

10 recordsLinked to original sources
PubMed2006

Histology of the nasal septal swell body (septal turbinate).

OBJECTIVE: To analyze the vascular and glandular elements of the nasal septal swell body (NSB) and quantitatively compare these to the inferior turbinate (IT) and non-swell body portion of septum. STUDY DESIGN: Fourteen healthy adults undergoing septoplasty and IT reduction were submitted to unilateral biopsies of the NSB, the adjacent inferior turbinate, and inferior septum. Photomicrography with morphometric analysis was used to determine the relative area proportions of each tissue type. RESULTS: NSB was rich in seromucinous glands (49.9% +/- 7.0%) compared to IT (19.9% +/- 5.5%), P < 0.01. Conversely, IT mucosa demonstrated increased area proportion of venous sinusoids (28.3 +/- 13.9) compared to NSB (10.0 +/- 6.0), P < 0.01. Inferior septal mucosa had glandular and vascular elements similar in proportion to that of NSB. CONCLUSIONS AND SIGNIFICANCE: NSB is a highly glandular structure of the anterior-superior septum, with moderate proportion of venous sinusoids. Located at the distal valve segment, the NSB appears structured for secretory function and vasoactive airflow regulation.

Adolescent↗
PubMed2006

Effect of a nutritional supplement on posaconazole pharmacokinetics following oral administration to healthy volunteers.

We conducted a randomized, crossover study in healthy adults to examine the effects of a nutritional supplement (Boost Plus) on posaconazole pharmacokinetics. In this study, coadministration of posaconazole with Boost Plus increased the maximum concentration of posaconazole in serum and area under the concentration-time curve from 0 to 72 h values 3.4- and 2.6-fold, respectively, compared to those for the fasted state.

Administration, Oral↗
PubMed2005

Aerodynamic effects of inferior turbinate reduction: computational fluid dynamics simulation.

OBJECTIVE: To investigate the aerodynamic consequences of conservative unilateral inferior turbinate reduction using computational fluid dynamics methods to accomplish detailed nasal airflow simulations. DESIGN: A high-resolution, finite-element mesh of the nasal airway was constructed from magnetic resonance imaging data of a healthy man. Steady-state, inspiratory airflow simulations were conducted at 15 L/min using the techniques of computational fluid dynamics. INTERVENTION: Circumferential removal of 2 mm of soft tissue bulk along the length of the left inferior turbinate was modeled. MAIN OUTCOME MEASURES: Nasal airflow distribution and pressure profiles were computed before and after simulated left inferior turbinate reduction. RESULTS: Simulated inferior turbinate reduction resulted in a broad reduction of pressure along the nasal airway, including the regions distant from the inferior turbinate vicinity. In contrast, relative airflow changes were regional: airflow was minimally affected in the valve region, increased in the lower portion of the middle and posterior nose, and decreased dorsally. CONCLUSION: Use of computational fluid dynamics methods should help elucidate the aerodynamic significance of specific surgical interventions and refine surgical approaches to the nasal airway.

Computer Simulation↗
PubMed2005

Oral bioavailability of posaconazole in fasted healthy subjects: comparison between three regimens and basis for clinical dosage recommendations.

BACKGROUND AND OBJECTIVE: Posaconazole is a potent, extended-spectrum triazole antifungal agent currently in clinical development for the treatment of invasive fungal infections. This study was conducted to compare the bioavailability and resulting serum concentrations of posaconazole 800 mg following administration of three different dose regimens to fasting adults. STUDY DESIGN: This was a randomised, open-label, three-way crossover study. METHODS: Subjects fasted 12 hours before and 48 hours after the administration of posaconazole oral suspension (800 mg) given as a single dose (regimen A), 400 mg every 12 hours (regimen B) or 200 mg every 6 hours (regimen C). Plasma posaconazole concentrations were determined for 48 hours after the initial dose and subjects completed a 1-week washout period between treatment regimens. A one-compartment oral model with first-order rate of absorption and first-order rate of elimination was fitted to the plasma concentration-time data. Differences in exposure were investigated by allowing the bioavailability fraction to vary among regimens. STUDY PARTICIPANTS: A total of 18 healthy men were enrolled in and completed the study. MAIN OUTCOME MEASURES AND RESULTS: Posaconazole relative bioavailability was estimated to be significantly different among regimens (p < 0.0001) and increased with the number of doses, such that regimen B/regimen A = 1.98 +/- 0.35, representing a 98% increase, and regimen C/regimen A = 3.20 +/- 0.69, or a 220% increase. With use of the one-compartment model, the population steady-state values for area under the concentration-time curve over 24 hours were predicted to be 3900, 7700 and 12 400 microg.h/L, with average plasma concentrations of 162, 320 and 517 microg/L for regimens A, B and C, respectively. CONCLUSION: These data suggest that divided daily dose administration (every 12 or 6 hours) significantly increases posaconazole exposure under fasted conditions.

Administration, Oral↗
PubMed2005

Partial inferior turbinectomy using the microdébrider.

BACKGROUND: A microdébrider was selected to accomplish partial inferior turbinectomy, allowing for controlled and rapid removal of hypertrophic soft tissue while preserving the general turbinate form. OBJECTIVE: To assess the clinical outcome, healing, and any adverse consequences from the microdébrider partial turbinectomy procedure. SETTING: A public hospital in north-central Israel. DESIGN: A nonrandomized prospective study of 35 adults who were referred for nasal airway surgery, including turbinectomy. METHODS: All patients underwent bilateral inferior turbinate reduction with the microdébrider, with removal of mucosa from the medial and inferior portions of the inferior turbinates. Detailed follow-up was accomplished at 4 or more months postoperatively, including a visual analogue scale questionnaire and videoendoscopy. For seven patients, pre- and postoperative mucosal biopsies were available to evaluate healing and epithelial regeneration. RESULTS: Nasal endoscopy showed well-healed turbinate membranes and preservation of the turbinate form, with widening of the inferomedial nasal airway space. Subjective nasal patency improved after surgery, p < .01, and the subjective sense of smell was improved, p < .01, without associated crusting, pain, irritation, sneezing, or dryness. Postoperative biopsies showed subepithelial fibrosis and regenerated epithelium, generally of respiratory differentiation. CONCLUSION: Inferior turbinate reduction can be accomplished efficiently with the microdébrider device, without undue side effects. SIGNIFICANCE: Further experience and long-term follow-up with this technique are warranted.

Adult↗
PubMed2004

Effect of food on the relative bioavailability of two oral formulations of posaconazole in healthy adults.

AIMS: This randomized, crossover, single-dose study evaluated the relative oral bioavailability of posaconazole suspension and coprecipitate tablet formulations. Additionally, the study determined whether systemic exposure to posaconazole was affected by prandial status or by the fat content of a meal. METHODS: This was a randomized, open-label, four-way crossover, single-dose study in 20 healthy men. Posaconazole pharmacokinetics were evaluated over 72 h following a single oral dose of posaconazole suspension (200 mg/5 ml) administered with a high-fat meal, a nonfat breakfast, or after a 10 h fast, or posaconazole tablets (2 x 100 mg) administered with a high-fat meal. RESULTS: The posaconazole suspension showed a significant increase in bioavailability compared with the tablet (increase in AUC(0,72 h) = 137% (90% confidence interval (CI) 119%, 156% and Cmax = 123% (90% CI 104%, 146%). The mean increases in AUC(0,72 h) and Cmax values were about 400% when administered with a high-fat meal compared with administration of the suspension in the fasting state (AUC(0,72 h) 90% CI 343%, 448%; Cmax 90% CI 352%, 493%). Administration of the suspension with a nonfat meal enhanced exposure, resulting in an increase in AUC(0,72 h) of 264% (90% CI 231%, 302%) and in Cmax of 296% (90% CI 250%, 350%) relative to the fasted state. CONCLUSIONS: The suspension formulation of posaconazole was associated with enhanced systemic exposure and increased relative bioavailability compared with the tablet. Food substantially enhanced the rate and extent of posaconazole absorption in healthy subjects.

Administration, Oral↗