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Biomedical subjects

Anthony A Mikulec

Publications and source records attributed to Anthony A Mikulec.

13 recordsLinked to original sources

Operative management of a posterior semicircular canal dehiscence.

OBJECTIVE: The objective of this study was to describe the operative management of posterior canal dehiscence. METHODS: A transmastoid approach to and plugging of the posterior canal was performed for posterior semicircular canal dehiscence (PSCD). RESULTS: Postoperatively, the patient exhibited improvement in conductive hearing loss and vestibular symptoms. CONCLUSIONS: PSCD can cause symptoms identical to that of superior semicircular canal dehiscence. Successful PSCD plugging can be performed without visualization of the actual area of dehiscence.

Adult↗

Results after revision stapedectomy with malleus grip prosthesis.

Revision stapedectomy with a malleus grip prosthesis is a technically challenging otologic procedure. The prosthesis is usually longer and extends deeper into the vestibule than a conventional stapes prosthesis, creating the potential to affect the vestibular sense organs. The prosthesis also bypasses the ossicular joints, which are thought to play a role in protecting the inner ear from large changes in static pressure within the middle ear. The prosthesis is in close proximity to the tympanic membrane, thus increasing the risk for its extrusion. We reviewed our experience with revision stapedectomy with the Schuknecht Teflon-wire malleus grip prosthesis in 36 ears with a mean follow-up of 23 months. The air-bone gap was closed to within 10 dB in 16 ears (44%) and to within 20 dB in 26 ears (72%). The incidence of postoperative sensorineural hearing loss was 8% (3 ears). There were no dead ears. Extrusion of the prosthesis occurred in 1 case (3%). Nearly 50% of patients reported various degrees of vertigo or disequilibrium during the first 3 weeks after surgery. These vestibular symptoms resolved by 6 weeks in all but 1 case. We did not find evidence of damage to the inner ear due to the length of the prosthesis or due to the potential for direct transmission of changes in static pressures within the middle ear to the labyrinth. Our results are similar to those published in the literature for malleus attachment stapedectomy and conventional revision incus stapedectomy.

Adult↗

A method for intracochlear drug delivery in the mouse.

The confluence of two rapidly emerging research arenas - development of mouse models of human deafness and inner ear drug therapy for treatment and prevention of hearing loss - provides an opportunity for unprecedented approaches to study and treat deafness. Toward such goals, we have developed a method for intracochlear drug delivery in the mouse. The bulla was exposed using a ventral approach and the stapedial artery cauterized. An opening made into the inferior-medial aspect of the bulla, where the basal cochlear wall fuses with tympanic bulla, provided direct access to the scala tympani without separately opening the bulla or elevating auditory response thresholds. Cochlear responses, assayed by frequency-specific effects on ABRs and DPOAEs, were stable with infusion (1 microl/h) of an artificial perilymph solution (80 min). The glutamate receptor antagonist, CNQX (100 microM; 175 min), reduced ABR responses without affecting DPOAEs. Salicylate (5mM; 165 min) altered both. Both drugs had greatest effects at high frequencies, but distributed throughout the cochlea and were reversible. The safe delivery of drugs into the cochlea by this approach has immediate application in the study and treatment of various forms of human hearing loss that can be modeled in the mouse.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Operative management of superior semicircular canal dehiscence.

OBJECTIVE: To assess the outcomes of patients undergoing surgical management of superior semicircular canal dehiscence (SSCD). STUDY DESIGN: Retrospective review. METHODS: The medical records of all patients undergoing surgical treatment for SSCD at our institution between 2000 and 2004 were reviewed. RESULTS: Eleven patients underwent unilateral operative management via a middle fossa approach. Ten patients were treated successfully by canal plugging and one unsuccessfully by canal re-roofing. Plugging of SSCD provided resolution of sound- and pressure-induced nystagmus, autophony, and conductive hearing loss (HL). One patient experienced a mild high-frequency sensorineural HL and two patients experienced both a mild high-frequency sensorineural HL and a reduction in vestibular function. Two additional patients underwent exploration for SSCD but were found to have a thin layer of bone overlying the canal. CONCLUSIONS: Plugging of the SSCD, while efficacious in alleviating the symptoms of the disease, may cause loss of labyrinthine function beyond the superior canal.

Adult↗

Perioperative steroids in tonsillectomy using electrocautery and sharp dissection techniques.

OBJECTIVE: To determine the effect of preoperative dexamethasone sodium phosphate administration on posttonsillectomy morbidity for electrocautery ("hot") and sharp ("cold") dissection techniques. DESIGN: Prospective, randomized, double-blind study. SETTING: University pediatric hospital and county teaching hospital. Subjects A total of 219 children, aged 9 months to 12 years, undergoing tonsillectomy. Intervention Participants who underwent tonsillectomy were randomly assigned to receive either intravenous dexamethasone sodium phosphate (1 mg/kg) or placebo. OUTCOME MEASURES: Pain scores, oral intake, and emesis on postoperative day (POD) 1. RESULTS: A total of 106 subjects (62 undergoing hot and 44 cold tonsillectomies) received preoperative steroids, and 113 (56 hot and 57 cold tonsillectomies) received placebo. On POD 1, pain scores reported by patients (P =.02), parents (P =.002), and physicians (P<.001) were significantly lower in subjects receiving steroids than in those receiving placebo. Emesis was reduced from a mean of 2.1 (placebo group) to 1.2 episodes (steroid group) (P =.02). Oral intake improved from 24.5% of normal diet (placebo) to 31.7% (steroid group) (P =.004). When all 4 groups were compared (cold placebo, cold steroid, hot placebo, and hot steroid), pain scores reported by physicians and parents were significantly lower in the cold steroid group than in the other groups. CONCLUSIONS: Perioperative dexamethasone use reduces posttonsillectomy morbidity in pediatric patients in the early postoperative period after hot or cold tonsillectomy. The combination of steroid and cold dissection technique provided the greatest advantage in reducing posttonsillectomy subjective pain levels.

California↗

Superior semicircular canal dehiscence presenting as conductive hearing loss without vertigo.

OBJECTIVE: The objective of this study was to describe superior semicircular canal dehiscence (SSCD) presenting as otherwise unexplained conductive hearing loss without vestibular symptoms. STUDY DESIGN: Retrospective. SETTING: Tertiary referral center. PATIENTS: The study comprised 8 patients (10 ears), 5 males and 5 females aged 27 to 59 years. All 10 ears had SSCD on high-resolution computed tomography scan of the temporal bone. DIAGNOSTIC TESTS AND RESULTS: All 10 ears had significant conductive hearing loss. The air-bone gaps were largest in the lower frequencies at 250, 500, and 1000 Hz; the mean gaps for these 3 frequencies for the 10 ears were 49, 37, and 35 dB, respectively. Bone-conduction thresholds below 2000 Hz were negative (-5 dB to -15 dB) at one or more frequencies in 8 of the 10 ears. There were no middle ear abnormalities to explain the air-bone gaps in these 10 ears. Computed tomography scan and laboratory testing indicated lack of middle ear pathology; acoustic reflexes were present, vestibular evoked myogenic potentials (VEMPs) were present with abnormally low thresholds, and umbo velocity measured by laser Doppler vibrometry was above mean normal. Middle ear exploration was negative in six ears; of these six, stapedectomy had been performed in three ears and ossiculoplasty in two ears, but the air-bone gap was unchanged postoperatively. The data are consistent with the hypothesis that the SSCD introduced a third mobile window into the inner ear, which in turn produced the conductive hearing loss by 1) shunting air-conducted sound away from the cochlea, thus elevating air-conduction thresholds; and 2) increasing the difference in impedance between the oval and round windows, thus improving thresholds for bone-conducted sound. CONCLUSION: SSCD can present with a conductive hearing loss that mimics otosclerosis and could explain some cases of persistent conductive hearing loss after uneventful stapedectomy. Audiometric testing with attention to absolute bone-conduction thresholds, acoustic reflex testing, VEMP testing, laser vibrometry of the umbo, and computed tomograph scanning can help to identify patients with SSCD presenting with conductive hearing loss without vertigo.

Acoustic Impedance Tests↗

Association between osteoporosis and otosclerosis in women.

Similarities between osteoporosis and otosclerosis have been noted, including a similar association with the COL1A1 gene. Herein, the authors explore the possible clinical relationship between these two common disorders of bone. In this retrospective study, the medical charts of 100 women aged 50 through 75 years who had undergone stapedectomy for otosclerosis were reviewed and the prevalence of osteoporosis in these women was noted. Similarly, the prevalence of osteoporosis was determined in a control group of 100 women aged 50 to 75 years with presbycusis. Fifteen of 100 women with otosclerosis had a concomitant diagnosis of osteoporosis as compared with four of 100 women with presbycusis, yielding a significant clinical association (p = 0.007) between otosclerosis and osteoporosis. This study suggests an association between otosclerosis and osteoporosis, providing impetus and justification for future prospective clinical studies and related research.

Age Distribution↗

Growth factor profile of irradiated human dermal fibroblasts using a serum-free method.

Radiation therapy for cancer permanently damages tissue in the line of treatment. This study sought to establish a serum-free protocol to evaluate the growth of irradiated fibroblasts and to analyze the levels of basic fibroblast growth factor (bFGF) and transforming growth factor-beta (TGF-beta) compared with normal fibroblasts. One irradiated cell line of human dermal fibroblasts was established from an intraoperative specimen obtained from a patient who had undergone radiation therapy for head and neck cancer. Irradiated and normal fibroblasts were then plated in UltraCULTURE (serum and growth factor free), modified Webber's medium (bFGF 50 ng/ml, insulin-like growth factor 100 ng/ml), and Dulbecco's Modified Eagle Medium with 10% fetal bovine serum (serum with undefined basal growth factors). Irradiated cells were also seeded in UltraCULTURE with 50 and 100 ng/ml of bFGF. Cell counts were performed at 0, 1, 3, 5, and 7 days, and cell supernatants were assayed for bFGF and TGF-beta. Irradiated and normal fibroblasts exhibited stronger growth in modified Webber's medium than in Dulbecco's Modified Eagle Medium with 10% fetal bovine serum. Growth of irradiated fibroblasts under bFGF modulation was similar to their growth in Webber's medium. Furthermore, irradiated fibroblasts remained viable in a serum-free and growth factor-free environment for at least 7 days; however, their growth and autocrine growth factor production was less than that of normal cells. This confirms the results of previous studies suggesting that cells from irradiated tissue undergo cellular changes. This study provides an effective model for the first-line evaluation of agents to improve wound healing, and it helps to establish standard levels of bFGF and TGF-beta production for irradiated fibroblasts.

Cell Count↗

Triamcinolone stimulates bFGF production and inhibits TGF-beta1 production by human dermal fibroblasts.

BACKGROUND: Triamcinolone acetonide has been shown to decrease both cellular proliferation and collagen production by dermal fibroblasts. An alteration of cytokine levels may mediate these effects. OBJECTIVE: To delineate the effect of triamcinolone acetonide on both cellular proliferation and the production of basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1) by human fibroblasts grown in a serum-free in vitro model. METHODS: Human normal and keloid dermal fibroblasts were propagated in a serum-free in vitro model with exposure to 0, 5, 10, or 20 microm triamcinolone acetonide for 0, 24, 72, or 96 hours. Cell counts were determined by phase contrast microscopy. Levels of bFGF and TGF-beta1 in the supernatants were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: In our study, 20 microm triamcinolone acetonide caused statistically significant increases in the peak levels of bFGF for normal and keloid fibroblast cell lines (P < 0.05). It also caused statistically significant decreases in the level of TGF-beta1 for normal and keloid fibroblast cell lines. For the keloid fibroblasts, 10 microm triamcinolone acetonide also caused a statistically significant decrease in the level of TGF-beta1. CONCLUSION: We conclude from these results that triamcinolone acetonide increases the production of bFGF and decreases production of TGF-beta1 by human dermal fibroblasts.

Analysis of Variance↗

Autocrine growth factor production by fetal, keloid, and normal dermal fibroblasts.

OBJECTIVE: To evaluate differences in fibroblast autocrine growth factor production by human fetal, keloid, and normal adult dermal fibroblasts. DESIGN: Serum-free cell lines of fetal, keloid, and normal adult dermal fibroblasts were established. Cell counts were performed and supernatants collected at 4, 24, and 72 hours. Cell-free supernatants were quantitatively assayed for transforming growth factor beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF). RESULTS: Population doubling times for fetal, keloid, and normal adult fibroblasts were 120.0, 88.1, and 128.4 hours, respectively. Differences in population doubling times did not reach statistical significance. Statistically significant differences between TGF-beta1 levels from fetal and normal adult fibroblasts were seen at 24 and 72 hours. Significant differences between TGF-beta1 levels from keloid and normal adult fibroblasts were also seen at 24 and 72 hours. Fetal fibroblasts demonstrated higher levels of bFGF than normal adult fibroblasts at each time point, but these differences were not statistically significant. No significant differences were observed between keloid and normal adult bFGF levels. CONCLUSIONS: Both fetal and keloid fibroblasts produce significantly more TGF-beta1 than normal adult fibroblasts. Our data and the data of others suggest that fetal fibroblasts produce more bFGF than adult fibroblasts. The serum-free model we describe can be used to quantitatively measure autocrine growth factor production by cells that underlie clinically different types of wound healing. This model provides information that may allow us to better treat and prevent undesirable scarring.

Adolescent↗

The effect of silicone gel on basic fibroblast growth factor levels in fibroblast cell culture.

BACKGROUND: Topical silicone gel has shown promise in the treatment of hypertrophic and keloid scars. However, its mechanism of action remains undetermined. OBJECTIVE: To investigate whether the presence of silicone alters the secretion of basic fibroblast growth factor (bFGF), a key cytokine involved in the scar formation process. DESIGN: Serum-free fibroblast cell cultures were established from normal, keloid, and fetal skin, which heals without scarring, and exposed to silicone gel. Serial cell counts were performed, and supernatants were collected for bFGF quantification by enzyme-linked immunosorbent assay at 4, 24, 72, and 120 hours. RESULTS: Growth curves were similar and no statistically significant differences in population doubling times were observed between treated and untreated specimens. Statistically significant differences in bFGF levels between treated and untreated normal fibroblasts were observed at 24, 72, and 120 hours after cell culture initiation. Differences in bFGF levels between treated and untreated fetal fibroblasts that approached statistical significance were observed at 72 and 120 hours. CONCLUSIONS: These results suggest that silicone gel is responsible for increased bFGF levels in normal and fetal dermal fibroblasts. We postulate that silicone gel treats and prevents hypertrophic scar tissue, which contains histologically normal fibroblasts, by modulating expression of growth factors such as bFGF. Our data support the hypothesis that substances that favorably influence wound healing do so by correcting a deficiency or overabundance of the growth factors that orchestrate the tissue repair process.

Adolescent↗

Growth and growth factor production by human nasal septal chondrocytes in serum-free media.

BACKGROUND: Tissue-engineered human cartilage offers vast possibilities as a source of graft implant material for reconstructive surgery. Serum-supplemented growth media is successful in supporting chondrocyte proliferation in vitro. Serum, however, contains exogenous growth factors that hamper the identification and quantification of growth factors autogenously produced by chondrocytes. We explore the possibility of using a commercially available serum-free medium UltraCULTURE as an alternative to modified Webber's medium (MWM), the standard media used in chondrocyte cell culture. METHODS: Human nasal septal chondrocytes were grown in UltraCULTURE containing various concentrations of basic fibroblast growth factor (bFGF; 0, 1, 10, and 100 ng/mL) with or without insulin-like growth factor and compared with chondrocytes grown in MWM. Growth curves and transforming growth factor (TGF) beta 1 production were analyzed. RESULTS: We found no differences in the ability to sustain cell viability in culture between the two base media types. We also found no statistically significant differences in TGF-beta 1 production by chondrocytes grown in either system. Finally, there were no statistically significant differences in chondrocyte proliferation between cultures supplemented with bFGF at 10 and 100 ng/mL. CONCLUSION: UltraCULTURE media is a cost-effective, serum-free alternative to standard media with compatible growth characteristics. It offers specific advantages over standard serum-containing media for the precise measurement of autogenous growth factor production by cultured chondrocytes. Furthermore, UltraCULTURE's serum-free environment would be ideal for safely producing tissue-engineered cartilage grafts.

Cartilage, Articular↗