Gerald Leonard

Evaluation of olfactory dysfunction in the connecticut chemosensory clinical research center

The olfactory test administered to patients at the Connecticut Chemosensory Clinical Research Center combines stability of outcome with sensitivity to variables known to affect olfaction (age, sex). The test, which pairs an odor threshold component with an odor identification component, readily resolves differences in function between patients and controls. It reveals differences in the distribution of functioning for various probable causes (nasal/sinus disease, postupper respiratory infection, and head trauma), proves sensitive to improvements in function caused by therapeutic intervention (ethmoidectomy, steroid administration for nasal/sinus disease), and correlates with objective signs of nasal/sinus disease (visual exam, x‐ray). The two components of the test agree well, though the odor identification component seems somewhat more sensitive than the threshold component as currently designed.

Characterization of cytokines present in middle ear effusions

Retention of inflammatory mediators and cells in the middle ear cleft during chronic otitis media with effusion (COME), results in ongoing inflammation with the potential for pathologic changes and hearing loss. Cytokines are glycoproteins produced by macrophages and other cells. Activities of cytokines include fever production, osteoclast, fibroblast, phagocyte and cytotoxic cell activation, regulation of antibody formation, and inhibition of cartilage, bone and endothelial cell growth. Using enzyme-linked immunospecific assays we measured levels of six cytokines in middle ear effusions (MEE) from children with COME. Significant levels of four cytokines: interleukin-1-beta (greater than 50 pg/ml), interleukin-2 (greater than 300 pg/ml), tumor necrosis factor-alpha (greater than 40 pg/ml), and gamma-interferon (greater than 6.25 pg/ml) were found in 51%, 54%, 63%, and 19% of MEE, respectively. In contrast, levels of a fifth cytokine, granulocyte-macrophage colony-stimulating factor, and a sixth cytokine, interleukin-4, were undetectable. Age was observed to have a significant effect on the levels of specific cytokines. Interleukin-1 (IL-1) correlated inversely (P less than .02) with age such that the younger the child, the higher the level of IL-1 in MEE. Tumor necrosis factor-alpha (TNF) correlated directly (P less than .005) with age such that the older the child, the higher the level of TNF in MEE. Children undergoing tympanostomy on multiple occasions had average MEE TNF levels (234.2 +/- 109.1 pg/mg total protein) that were nearly 14 times higher (P less than .005) than those from children undergoing their first tympanostomy (16.9 +/- 3.0 pg/mg total protein). Thus IL-1 correlated with the early stages of COME, while TNF correlated with persistence of disease. The presence of these cytokines in MEE may be responsible for the mucosal damage, bone erosion, fibrosis, and resulting hearing loss seen in some cases of COME.

Mandibular involvement by oral squamous cell carcinoma

Detecting mandibular bone involvement by oral carcinoma prior to definitive therapy poses a difficult problem for the head and neck surgeon. A retrospective study of 104 patients who underwent segmental mandibular resection for oral squamous cell carcinoma was undertaken to detect the incidence of mandibular bone involvement. Specimens from 23 patients (22%) demonstrated tumor invasion on decalcified histologic examination. Histologic evidence of bone involvement was correlated with the site of lesion, stage of the disease, the grade of tumor, the clinical impression of bone involvement, and the presence or absence of neck disease. Bone invasion on histologic examination was also compared with preoperative bone scans and radiographs. The data obtained demonstrates significant mandibular involvement with alveolar tumors and lesions clinically adjacent to the mandible. There was also a high incidence of histologic bone involvement in patients who had radiologic or bone scan evidence of tumor erosion. We support segmental mandibulectomy on the basis of providing adequate tumor margins for patients fulfilling these criteria.

Role and feasibility of psychomotor and dexterity testing in selection for surgical training

The practice of Surgery has undergone major changes in the past 20 years and this is likely to continue. Knowledge, judgement and good technical skills will no longer be enough to safely practice surgery and interventional procedures. Fundamental abilities (e.g. psychomotor skills, visuospatial ability and depth perception) are critically important for catheter‐based interventions, NOTES, robotic surgery and other procedural interventions of the future. Not all individuals possess the same amount of these innate fundamental abilities and those less endowed are likely to struggle during surgical training and thereafter in surgical practice. In contrast to other high‐skill professions/industries (e.g. aviation) we do not have a tradition of testing prospective surgical trainees for abilities/attributes that we now recognize as being important for surgical practice. Instead, we continue to rely on surrogate markers of future potential (e.g. academic record). However, many studies have shown that psychomotor ability is an important predictor of both learning rate and performance for complex laparoscopic tasks. Psychomotor skills, visuospatial ability and depth perception can all be tested objectively by validated tests. At the Royal College of Surgeons in Ireland, all short‐listed candidates for Higher Surgical Training now undergo formal testing of both technical skills and fundamental abilities (psychomotor skills, visuospatial ability and depth perception). Reports on each candidate’s performance are supplied to the interview committee. Furthermore, a prospective database is being kept for correlation with future surgical performance. We believe that selection into surgical training should take account of attributes that we know are important for safe and efficient surgical practice.

Distortion-Product and Click-Evoked Otoacoustic Emissions of Preterm and Full-Term Infants

Abstract Full-term and preterm infants were evaluated with click-evoked and distortion product otoacoustic emissions [CEOEs and DPOEs]. The CEOEs and DWEs recorded from each individual ear were analyzed by calculating the root-mean-square levels within half-active bands. The fail criterion of the OE tests was that the half-active RMS DPOE or CEOE levels of an ear under test were below the 10th percentile of full-term newborns in two or more bands. The DPOE data were collected from 118 ears of 61 premature babies; 80 (68%] ears passed the DPOE test, 30 [25%] ears without middle ear effusions failed the test, and 8 (7%] ears with effusions also failed. The CEOE data were collected from 128 ears of 65 premature babies; 102 (80%) ears passed the CEOE test, 18 (14%) ears without middle ear effusions failed the test, and 8 (6%] ears with effusions also failed. In 23 of 80 ears (29%) that passed the DWE test and in 23 of 102 ears (23%] that passed the CEOE test, RMS OE levels of preterm infants were above the 90th percentile of full-term newborns. The analyses of the combined DPOE and CEOE data obtained from a group of 25 ears of full-term newborns and from a group of 72 ears of preterm babies showed statistically significant correlations between the DPOE and CEOE root mean-square levels in each of the half-octave bands in the 1.4 to 4 kHz region. For 42 preterm infants tested with auditory brain stem response [ABR), specificity was 86% for CEOE and 74% for DPOE. All infants who failed the ABR also failed OE tests. To the best of our knowledge, this study is the first using combined DWEs, CEOEs, and ABRs for preterm babies. It showed the feasibility of DWEs and CEOEs for this population.

Murine model of otitis media with effusion: Immunohistochemical demonstration of il-1α antigen expression

Recent studies have suggested that cytokines likely play a central role in the formation and maintenance of otitis media with effusion (OME). Currently, there is no immunologically defined animal model for the study of cytokines as they contribute to the formation of OME. In the present study, a murine model of OME, using eustachian tube blockage via an external surgical approach, was developed. The murine model temporal bone histology appears to mimic the histology found in chronic otitis media with effusion in humans. Additionally, using this murine model, interleukin‐1α (IL‐1α) expression was detected in the middle ear using standard immunohistochemical techniques. IL‐1α seemed localized to the epithelial lining of the middle ear as well as 5% to 10% of inflammatory cells. This model should provide the necessary tool to further study the immunologic aspects of OME.

Characterization of the Eosinophil Chemokine Rantes in Nasal Polyps

Previous studies have demonstrated that the cytokine RANTES (Regulated And Normal T cell Expressed and Secreted) has been shown to be a potent mediator of eosinophil Chemotaxis in vitro and of leukocyte recruitment. Because eosinophils are the hallmark cells in nasal polyposis, we hypothesize that RANTES is locally produced within the nasal polyp microenvironment and is responsible for the eosinophil recruitment seen in nasal polyposis. To begin to test this hypothesis, we evaluated nasal polyps from 17 patients and 3 control specimens for distribution and content of RANTES using immunohistochemical techniques and enzyme-linked immunosorbent assay technology. Our immunohistochemical studies demonstrated that in nasal polyposis, RANTES antigen staining occurred predominantly within eosinophils and epithelial cells. To quantify the relative levels of RANTES in normal and nasal polyp specimens, tissue homogenates were prepared, quantified, and normalized to protein levels. We detected RANTES in all 17 nasal polyp tissue homogenates (566 ± 16 pg/mg total protein). The RANTES levels in nasal polyp homogenates were nearly 40-fold higher man the RANTES levels in normal tissue (15.7 ± 28.2 pg/mg total protein). Thus, it appears that increased expression of RANTES by eosinophils and epithelial cells within the nasal polyp microenvironment promotes eosinophil recruitment and activation within nasal polyps. We hypothesize that RANTES induces increased recruitment and activation of eosinophils, presumably contributing to the increased tissue changes associated with nasal polyposis.

Otoacoustic emissions in normal and hearing-impaired children and normal adults.

Although distortion‐product otoacoustic emissions (DPOEs) have been studied in adults recently, there is little information regarding them in young children. DPOEs and click‐evoked otoacoustic emissions (CEOEs) were measured from a same group of normal and hearing‐impaired children (age 4 through 10 years) and normal adults (age 22 through 29 years). Measurements of DPOEs in 13 childrens ears with normal hearing showed higher levels of emissions in the 700‐ to 1400‐Hz and 5.7‐kHz regions relative to the data obtained in 10 normal adult ears. The 22 ears of children with sensorineural hearing loss demonstrated agreement between pure‐tone audiograms and “DPOE audiograms.” Measurements of CEOEs revealed that the average level of emission in 15 normal‐hearing childrens ears was slightly lower than that previously obtained in newborns, but slightly higher than that of adults. In children, the CEOE spectral components in the 4‐ to 6‐kHz region were lower than in newborns, but higher than in adults. These results support the view that the DPOEs and CEOEs comprise a valuable tool in assessment of cochlear function in subjects of all ages.

Interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor expression in nasal polyps☆

PURPOSE Nasal polyps (NP) are grape-like clusters of chronically inflamed tissue. Little is known about the underlying cells and cytokines involved in nasal polyposis. For the present study, we hypothesize that elevated tissue levels of interleukin-3 (IL-3), interleukin-5 (IL-5), and granulocyte-macrophage colony-stimulation factor (GM-CSF) contribute to eosinophil recruitment and activation in NP. MATERIALS AND METHODS To begin to test this hypothesis, we evaluated IL-3, IL-5, and GM-CSF levels and distributions in nasal polyp specimens obtained intraoperatively from 13 patients and two normal controls. For these studies, nasal polyp levels were determined by enzyme-linked immunosorbent assay (ELISA), and IL-3, IL-5, and GM-CSF distribution was determined by immunohistochemistry. RESULTS Immunohistochemical staining of the NP indicated that in all 13 patient samples, IL-3, IL-5, and GM-CSF were associated with infiltrating cells, primarily eosinophils, in the NP. Quantitation of IL-3, IL-5, and GM-CSF in NP tissue homogenates indicated that IL-3, IL-5, and GM-CSF levels were evaluated in the NP tissues when compared with control tissues. Additionally, elevation of individual cytokines correlated with previous polypectomy (IL-3), steroid use (IL-3, IL-5, and GM-CSF), asthma (IL-5), and age (GM-CSF). CONCLUSION These data support our hypothesis that IL-3, IL-5, and GM-CSF are likely to play a key role in eosinophil recruitment/activation and NP formation and support recently advanced theories that cytokines play a key role in the pathogenesis of this disease.

Prospective clinical investigation of the relationship between idiopathic benign paroxysmal positional vertigo and bone turnover: a pilot study.

Idiopathic benign paroxysmal positional vertigo (BPPV) is a strong indicator of decreased bone density (osteopenia/osteoporosis) in postmenopausal women, and there is a correlation between BPPV and serum levels of biochemical markers of bone turnover.