Biomedical subjects
Publications and source records attributed to Scott K Thompson.
Success in microtia surgery requires meticulous patient education, planning, technique, and follow-through. When these principles are followed, excellent results as well as tremendous satisfaction are achievable for both the patient and surgeon.
OBJECTIVE: To examine the effects of estrogen suppression on age-related changes in distortion product otoacoustic emissions (DPOAEs) and contralateral suppression (CS) of DPOAEs in CBA mice. STUDY DESIGN AND SETTING: Young CBA mice received a slow-release shoulder implantation of either tamoxifen or placebo. Serial DPOAEs and CS of DPOAEs were obtained at 3-week intervals over a period of 9 weeks. RESULTS: Although DPOAEs were maintained over the study interval, CS of DPOAEs decreased significantly with age in the experimental group. No such declines were observed in either the control animals or the untreated male mice. CONCLUSIONS: Estrogen suppression negatively affects the MOC efferent feedback system. SIGNIFICANCE: Our results support the hypothesis that estrogen plays an important role in the maintenance of auditory integrity. Additionally, our findings raise intriguing questions about auditory effects of hormonal shifts in humans resulting from menopause, hormone supplements such as oral contraceptives, and hormone replacement therapy as well as antiestrogens.
Inhibitors of human methionine aminopeptidase type 2 (hMetAP2) are of interest as potential treatments for cancer. A new class of small molecule reversible inhibitors of hMetAP2 was discovered and optimized, the 4-aryl-1,2,3-triazoles. Compound 24, a potent inhibitor of cobalt-activated hMetAP2, also inhibits human and mouse endothelial cell growth. Using a mouse matrigel model, this reversible hMetAP2 inhibitor was also shown to inhibit angiogenesis in vivo.
Substituted 3-(phenylamino)-1H-pyrrole-2,5-diones were identified from a high throughput screen as inducers of human ATP binding cassette transporter A1 expression. Mechanism of action studies led to the identification of GSK3987 as an LXR ligand. GSK3987 recruits the steroid receptor coactivator-1 to human LXRalpha and LXRbeta with EC(50)s of 40 nM, profiles as an LXR agonist in functional assays, and activates LXR though a mechanism that is similar to first generation LXR agonists.
Liver X receptor (LXR) nuclear receptors regulate the expression of genes involved in whole body cholesterol trafficking, including absorption, excretion, catabolism, and cellular efflux, and possess both anti-inflammatory and antidiabetic actions. Accordingly, LXR is considered an appealing drug target for multiple indications. Synthetic LXR agonists demonstrated inhibition of atherosclerosis progression in murine genetic models; however, these and other studies indicated that their major undesired side effect is an increase of plasma and hepatic triglycerides. A significant impediment to extrapolating results with LXR agonists from mouse to humans is the absence in mice of cholesteryl ester transfer protein, a known LXR target gene, and the upregulation in mice but not humans of cholesterol 7alpha-hydroxylase. To better predict the human response to LXR agonism, two synthetic LXR agonists were examined in hamsters and cynomolgus monkeys. In contrast to previously published results in mice, neither LXR agonist increased HDL-cholesterol in hamsters, and similar results were obtained in cynomolgus monkeys. Importantly, in both species, LXR agonists increased LDL-cholesterol, an unfavorable effect not apparent from earlier murine studies. These results reveal additional problems associated with current synthetic LXR agonists and emphasize the importance of profiling compounds in preclinical species with a more human-like LXR response and lipoprotein metabolism.
Mifepristone is a non-selective antagonist of 3-oxosteroid receptors with both abortifacient and anti-endometriotic activities. Non-steroidal mimetics of mifepristone and progesterone are important templates for modulation of the progesterone receptor (PR). For our PR program, we sought an unexplored, synthetically accessible non-steroidal mimetic of mifepristone, suitable for parallel synthesis of analogues. Docking of compounds into a PR homology model identified 4-substituted pyrazolines, which, when synthesized and tested, exhibited functional antagonism of PR.
OBJECTIVE: Although many studies have examined the effects of systemic corticosteroid therapy (SCT) on the clinical course of infectious mononucleosis (IM), few have evaluated the influence of these studies on treatment patterns and outcomes. The purpose of this study was to review current therapeutic strategies and outcomes in uncomplicated and complicated IM. DESIGN: Retrospective case series. SETTING: Tertiary care center. PATIENTS: We identified 206 immunocompetent patients with IM diagnosed during the previous 5 years. Patient information, including age, sex, history and physical findings at presentation, pertinent laboratory data, management practices, and treatment outcomes, were analyzed. INTERVENTIONS: Systemic corticosteroid therapy was used in 44.7% of patients. Evaluation of treatment indications for SCT revealed that 8.0% of the study population qualified by traditional criteria for the use of corticosteroids; 92.0% of patients received SCT for other indications. Factors associated with the observed increase in corticosteroid use included a history of repeat visits, inpatient admission, and otolaryngology consultation. MAIN OUTCOME MEASURES: Diagnosis was made on the basis of a positive heterophil antibody test (monospot test) with appropriate clinical findings (97.5% of patients) or by the presence of lymphocytosis with appropriate clinical findings (2.4% of patients). RESULTS: Systemic corticosteroid therapy was not positively associated with fever, decreased oral intake, tonsillar hypertrophy, or duration of symptoms. No significant differences in incidence of disease complications, rates of hospital admission, or length of hospital stay were noted between the steroid and nonsteroid treatment groups. CONCLUSIONS: Despite consistent and uniform acceptance in the medical literature that SCT in the setting of IM should be reserved for patients with impending airway obstruction, corticosteroids continue to be used on a much broader scale at this tertiary care institution. This observation suggests that clinicians see value in SCT for treatment of IM beyond the classically accepted reasons. Moreover, despite previous reports of possible adverse consequences of SCT in IM, our review failed to demonstrate any such trend.
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OBJECTIVES/HYPOTHESIS: The purpose of the study was to evaluate the effectiveness of external auditory canal foreign body removal attempts by health care practitioners and to explore outcomes of patients with unsuccessful initial removal attempts. STUDY DESIGN: Retrospective case series. METHODS: A case series of patients presenting with external auditory canal foreign body to the emergency department of the authors' institution (Strong Memorial Hospital, University of Rochester Medical Center) over a 3-year period was studied retrospectively. Medical records were reviewed, and information including age at presentation, type of foreign body, side of presentation, length of time in place, signs and symptoms at presentation, management practices, and outcomes was recorded. RESULTS: One hundred sixty-two patients with a diagnosis of external auditory canal foreign body were identified. Emergency personnel successfully managed 67% of patients using direct visualization techniques, and 33% required otolaryngological consultation. Otolaryngologists used otomicroscopy with standard otological instruments as their mainstay of management. Analysis of successfully managed emergency department cases revealed that 82% of foreign bodies were irregularly shaped objects with soft, graspable parts. Conversely, 72% of foreign bodies in otolaryngology referrals were firm, rounded objects such as beads and beans. Analysis of patients referred to otolaryngologists revealed a requirement for removal under anesthesia of 19%. Patients with a history of one or more removal attempts before emergency department evaluation universally failed further direct visualization techniques. A disproportionate number of these patients eventually required operative intervention and/or had tympanic membrane perforation. Patients with a history of previous removal attempt(s) who were referred directly to otolaryngologists were more likely to be successfully managed without general anesthesia. CONCLUSION: Emergency room personnel successfully manage the majority of patients with foreign bodies of the external auditory canal. For patients with firm, rounded objects, direct otolaryngology consultation without further manipulation should be strongly considered. Patients who have had previous removal attempts should not undergo further manipulation in the emergency department but rather should be referred directly to an otolaryngologist.