Kenneth H. Lee

Effect of Basic Fibroblast Growth Factor; An In Vitro Study of Tendon Healing

The effect of basic fibroblast growth factor on the proliferative and chemotactic response of cultured rat patellar tendon fibroblasts was studied in an in vitro wound closure model. In quiescent confluent fibroblast culture, a uniform cell free zone, or wound, was generated mechanically as an in vitro wound. The width of the cell free zone was measured at 0, 6, 12, and 24 hours after the injury, in the presence of 0, 2, 10, or 50 ng/mL of basic fibroblast growth factor. Basic fibroblast growth factor, at a concentration of 10 ng/mL, significantly accelerated wound closure, resulting in almost complete closure by 24 hours after the injury. Basic fibroblast growth factor, at a concentration of 2 ng/mL, significantly enhanced cell proliferation as estimated by 5-Bromo-2′-deoxyuridine incorporation, but increasing the concentration of the growth factor to 50 ng/mL did not show additional improvement. Thus, the enhancement of wound closure by basic fibroblast growth factor may be caused by the cell proliferative response, rather than by chemotaxis.

Hair cell regeneration in the bird cochlea following noise damage or ototoxic drug damage

Hair cells are sensory cells that transduce motion into neural signals. In the cochlea, they are used to detect sound waves in the environment and turn them into auditory signals that can be processed in the brain. Hair cells in the cochlea of birds and mammals were thought to be produced only during embryogenesis and, once made, they were expected to last throughout the lifetime of the animal. Thus, any loss of hair cells due to trauma or disease was thought to lead to permanent impairment of auditory function. Recently, however, studies from a number of laboratories have shown that hair cells in the avian cochlea can be regenerated after acoustic trauma or ototoxic drug damage. This regeneration is accompanied by a repair of the sensory organ and associated tissues and results in a recovery of auditory function. In this review, we examine and compare the structural events that lead to hair cell loss after noise damage and ototoxic drug damage as well as the processes involved in the recovery of the epithelium and the regeneration of the hair cells. Moreover, we examine functional recovery and how it relates to the structural recovery. Finally, we investigate the evidence for the hypothesis that supporting cells in the basilar papilla act as the progenitor cells for the regenerated hair cells and examine the cellular events required to stimulate the progenitor cells to leave the quiescent state, re-enter the cell cycle, and divide.

Potential role of BFGF and retinoic acid in the regeneration of chicken cochlear hair cells

Messenger RNAs (mRNA) of several growth factor receptors and relate genes were examined with reverse transcriptase polymerase chain reaction (RT-PCR) in normal and noise-damaged chicken basilar papillae (BP). Analysis of the amplification products indicated the presence of mRNAs for epidermal growth factor receptor (EGFR), fibroblast factor receptor (FGFR), insulin-like growth factor receptor (IGFR), insulin receptor (IR), retinoic acid receptor beta (RAR beta), retinoic acid receptor gamma (RXR gamma), and basic fibroblast growth factor (BFGF) in both normal and noise-damaged BP. The RT-PCR products generated were characterized by size and sequencing analysis to confirm the identities of the target molecules. The subcellular localization of the mature protein analogs for EGFR, FGFR, IGFR, RAR beta, and BFGF were identified using fluorescence immunocytochemistry and confocal laser scanning microscopy. These experiments indicated that EGFR is present in the stereociliary bundles in the hair cells, IGFR is not present in the cells of the BP, BFGF localizes in the nuclei of supporting cells in the BP, but not hair cells or hyaline cells, and that RAR beta localizes in the perinuclear regions of hair cells. The subcellular distributions of these proteins were consistent in both noise-damaged and control BP. FGFR, in contrast, changed its distribution in the tissue after noise damage. In normal BP, FGFR is concentrated in the stereocilia of hair cells. However, in damaged regions of noise-exposed chick cochleae, FGFR is heavily expressed in the expanded apical regions of the supporting cells. These findings suggest that BFGF and retinoic acid may potentially play a role in the mechanisms which regulate the regeneration of chicken cochlear hair cells.

Regeneration of hair cells in the vestibulocochlear system of birds and mammals

Regeneration of hair cells leads to a structural and functional recovery in the mature avian vestibular and auditory sensory epithelia. This regeneration replaces hair cells that have been lost as a result of noise damage, ototoxic drug poisoning, or other trauma. Recent findings suggest that it may be possible to induce a similar mechanism for repair in the vestibular and auditory epithelia of mammals, including humans.

Cochlear implantation in children with enlarged vestibular aqueduct

To determine audiometric outcomes and complications of cochlear implantation in patients with enlarged vestibular aqueduct (EVA).

Cochlear Implantation in Children With Cochlear Nerve Absence or Deficiency

Objective: To evaluate speech perception after cochlear implantation in children with cochlear nerve absence or deficiency. Methods: A retrospective case review was performed to identify children who underwent cochlear implantation with cochlear nerve absence or deficiency. The cochlear nerve was evaluated by high-resolution three-dimensional T2-weighted fast spin echo MR in the oblique sagittal and axial planes. A deficient cochlear nerve was defined as a cochlear nerve that is smaller in diameter when compared with the adjacent facial nerve in the midportion of the internal auditory canal. The cochlear nerve was considered absent if there was no imaging evidence of a cochlear nerve. Speech awareness threshold and the speech perception category score were used to measure speech perception after cochlear implantation. Results: Seven children who underwent cochlear implantation in an ear without imaging evidence of a cochlear nerve were identified. One child developed early closed-set speech recognition. The other 6 children developed only speech detection or pattern perception. Two children underwent cochlear implantation with a deficient cochlear nerve. One developed consistent closed-set word recognition and the other developed early closed-set word recognition. The mean follow-up time for all patients was 3.8 years (range, 1.1-7.1 yr). Conclusion: Cochlear nerve deficiency is not an uncommon cause for profound sensorineural hearing loss and presents a challenge in the decision-making process regarding whether to proceed with a cochlear implant. Children with a deficient but visible cochlear nerve on magnetic resonance image can expect to show some speech understanding after cochlear implantation; however, these children do not develop speech understanding to the level of implanted children with normal cochlear nerves. Children with an absent cochlear nerve determined by magnetic resonance imaging can be expected to have limited postimplantation sound and speech awareness.

Labyrinthitis ossificans: How accurate is MRI in predicting cochlear obstruction?

Objective: To determine the accuracy of preoperative MRI in predicting cochlear obstruction in pediatric patients with a history of bacterial meningitis. Methods: A case series with chart review was performed at a tertiary care multidisciplinary cochlear implant program. Forty-five children with hearing loss that resulted from bacterial meningitis were implanted from 1991 to 2006. Twenty-five children had preoperative MRI with high-resolution axial T2-weighted images to assess for cochlear patency. Results: Seventeen of 25 patients (68%) had surgical evidence of cochlear obstruction. Six patients (37.5%) required circummodiolar drill-outs, and one patient (6.25%) underwent placement of a double array cochlear implant. The nine remaining patients (56%) with cochlear obstruction required removal of fibrous tissue or drilling of the inferior basal turn, but did not require manipulation of the ascending basal turn to achieve full electrode insertion. The sensitivity, specificity, and positive and negative predictive value of MRI predicting intraoperative cochlear obstruction with 95 percent confidence intervals was 94.1 percent (71–99), 87.5 percent (47–99), 94.1 percent (71–99) and 87.5 percent (47–99), respectively. Conclusion: Preoperative high-resolution T2 MRI may be useful in predicting cochlear obstruction in patients with a prior history of bacterial meningitis.

Role of balloon dilation in the management of adult idiopathic subglottic stenosis.

Objectives We evaluated the efficacy of balloon dilation for adjunctive and symptomatic management of isolated idiopathic subglottic stenosis in adults. Methods Adults with airway obstruction symptoms classified as idiopathic subglottic stenosis based on history and findings of a single discrete stenotic area on microlaryngoscopy and bronchoscopy were included in this series. Patients who met these criteria underwent dilation with a 10- to 14-mm balloon in a single procedure or in 2 consecutive dilations within 7 days. The patients were followed for up to 30 months after dilation. Results Six patients met the criteria. One of the 6 had prior laser treatments and a cricotracheal resection. One patient had a previous scar band lysis procedure. The remaining 4 patients had no prior procedures. The airway sizes prior to dilation ranged from a 2.5 endotracheal tube to a 5.0 endotracheal tube. In all cases the airway was dilated to 2.0 to 3.5 endotracheal tube sizes larger than the initial size. To date, 4 patients have been followed for 10 to 30 months without symptoms of recurrent airway stenosis. One patient was symptom-free for 22 months, then presented with progressive airway difficulty following an upper respiratory tract infection, and has undergone a repeat dilation. No patients had adverse effects or complications from the procedure. Conclusions Balloon dilation of idiopathic subglottic stenosis in adults is a relatively safe and effective method to manage this disease entity for cases of isolated and discrete lesions. Patients who underwent a single procedure have remained symptom-free for up to 30 months after balloon dilation.

Contemporary assessment and management of congenital cholesteatoma.

Purpose of reviewOnly 2–4% of cholesteatomas presenting to pediatric otologists are congenital in origin. Disease severity can range from intratympanic pearls to middle ear and mastoid obliteration. Recently, highlighted variations of this rare disorder warrant a systematic approach to disease assessment and surgical decision making. This review provides a comprehensive method to diagnose and manage congenital cholesteatoma based on current literature. Recent findingsThe holding theory of the origin of congenital cholesteatomas is that they arise from retained epithelial cell rest. Primary development can vary among sites within the middle ear and mastoid. ‘Open’ and ‘closed’ varieties have been proposed. However, disease severity depends on location, patient age, ossicular integrity, and number of anatomic sites involved. These variables have inspired the development of staging systems whereby appropriate surgical approaches can be designed. Computed tomography (CT) scans are necessary and continue to be the best radiographic tool for surgical planning. Over 30% of congenital cholesteatomas can be extirpated through a transcanal approach. Involvement of the posterior quadrant, over three anatomic subsites, or the mastoid cavity obligates standard canal wall-up techniques. Canal wall-down procedures are rarely required. SummaryCongenital cholesteatomas frequently extend beyond the typically described anterosuperior location of the middle ear. Ossicular destruction, mastoid infiltration, and tympanic membrane rupture are encountered more frequently than previously thought. Advanced disease predominately occurs in older children and requires sophisticated assessment and surgical planning beyond removing a simple keratin cyst.

Comparison of microtia reconstruction outcomes using rib cartilage vs porous polyethylene implant.

IMPORTANCE Auricular reconstruction is a unique blend of cosmesis and functionality. The choice of the optimal framework material to use is an important decision for the patient with microtia. OBJECTIVE To evaluate and compare the outcomes of reconstruction of microtia using porous polyethylene implants and rib cartilage grafts. DESIGN, SETTING, AND PARTICIPANTS Retrospective medical record review from January 1, 2001, through December 31, 2012, at a tertiary academic institution. Thirty-five patients (36 ears) undergoing microtia repair were divided into groups using high-density porous polyethylene (17 ears), rib cartilage (17 ears), and both materials (2 ears). Only patients with completed repair were included in the analysis. EXPOSURES Reconstructive surgery for microtia. MAIN OUTCOME AND MEASURES We compared groups in terms of mean number of operations, age at treatment initiation, and complications (infection, extrusion, cartilage exposure, and pneumothorax). Photographs were graded by blinded observers to give each patient a score on protrusion, definition, shape, size, location, and color match. RESULTS The cartilage group was older than the polyethylene group (mean age, 8.0 vs 6.9 years; P = .23). The mean number of operations was 4.88 for the cartilage group vs 3.35 for the polyethylene group (P = .004). Two patients in the polyethylene group had postoperative infections and implant extrusion and underwent subsequent reconstruction with cartilage grafts. Patients in the cartilage group had no infection or extrusion; 1 had a minor cartilage exposure. No patient had pneumothorax. Patients in the polyethylene group had significantly better grades for ear definition and size match, whereas those in the cartilage group had a significantly better color match. Patients in the cartilage group had better protrusion and location outcomes, although the difference was not significant. CONCLUSIONS AND RELEVANCE Comparison of reconstruction with porous polyethylene implants and rib cartilage grafts showed neither material to be clearly superior. Polyethylene implants may achieve a better cosmetic outcome in the categories of ear definition, shape, and size with a higher risk for infection and extrusion. Patients in the cartilage group were older and underwent significantly more surgical procedures, which should factor into the decision on which technique to choose. LEVEL OF EVIDENCE 3.