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Biomedical subjects

Samuel H Selesnick

Publications and source records attributed to Samuel H Selesnick.

13 recordsLinked to original sources
PubMed2007

Protection against cisplatin-induced ototoxicity by adeno-associated virus-mediated delivery of the X-linked inhibitor of apoptosis protein is not dependent on caspase inhibition.

HYPOTHESIS: Gene therapy with an adeno-associated viral (AAV) vector encoding the X-linked inhibitor of apoptosis protein (XIAP) in an animal model of cisplatin-induced ototoxicity can elucidate apoptotic pathways in the inner ear. BACKGROUND: Cisplatin is limited clinically by ototoxicity associated with apoptosis in the inner ear. The relevant intracellular apoptotic pathways, however, are unknown. XIAP is an antiapoptotic protein that both inhibits caspases and reciprocally regulates the proapoptotic Smac/Omi proteins. AAV-mediated delivery of various XIAP mutants could distinguish between these antiapoptotic pathways in the ear and further the development of specific reagents for gene therapy- mediated prevention of cisplatin-induced ototoxicity. METHODS: We administered unilaterally through the round-window AAV-harboring genes encoding wild-type dXIAP, yellow fluorescent protein, or either of two dXIAP point mutants-one deficient in caspase inhibition (dXIAP-d) and the other additionally deficient in the binding of Smac/Omi (dXIAP-t). All rats received a 3-day systemic course of cisplatin. Functional hearing loss was measured by shifts in auditory brainstem response (ABR) thresholds after cisplatin treatment, and hair-cell loss was assessed by whole-mount phalloidin staining of cochlear turns. RESULTS: Uninjected ears universally displayed high-frequency-specific hair-cell loss and ABR threshold shifts upon cisplatin treatment. Although yellow fluorescent protein had no effect, ears injected with dXIAP exhibited 68% less ABR threshold shift at 32 kHz and 50% less basal-turn outer-hair-cell loss compared with contralateral untreated ears. This protection was maintained in ears injected with dXIAP-d but was abolished in those expressing dXIAP-t, which is incapable of blocking Smac/Omi. CONCLUSION: Hair-cell apoptosis induced by cisplatin involves the Smac/Omi pathway. Thus, gene therapy with either wild-type dXIAP or Smac/Omi-selective dXIAP-d may be effective to protect against cisplatin-mediated ototoxicity.

Animals↗
PubMed2006

AAV-mediated delivery of the caspase inhibitor XIAP protects against cisplatin ototoxicity.

HYPOTHESIS: Delivery of the gene encoding X-linked inhibitor of apoptosis (XIAP) using an adeno-associated viral (AAV) vector can protect against cisplatin-mediated ototoxicity. BACKGROUND: Cisplatin is a widely used chemotherapeutic agent with significant ototoxic side effects. One possible mechanism of toxicity is apoptotic death of many cochlear cell types. Acute treatment with inhibitors of caspases- enzymes critical for apoptosis- has been shown to prevent hearing loss in vivo, but is too short-acting for therapeutic use. Gene therapy provides a specific and chronic means of delivering potential therapeutic gents. Introducing an anti-apoptotic gene into the cochlea could provide long-term prophylaxis against the ototoxic effects of cisplatin. METHOD: Two groups of rats were treated with unilateral injection into the round window of AAV harboring a gene encoding either XIAP or green fluorescent protein (GFP). After at least two months of gene expression, auditory-brainstem-response (ABR) threshold shifts and outer-hair-cell (OHC) number were measured in these two groups of animals after 72-hour treatment with cisplatin. RESULTS: Consistent with previous reports, uninjected and AAV.GFP-injected ears displayed profound ABR threshold elevations and OHC loss after cisplatin treatment. Ears that had been injected with AAV encoding XIAP, however, were significantly protected from these effects: cisplatin-induced ABR-threshold shift and hair-cell loss were attenuated by as much as 78% and 45%, respectively, when compared with contralateral (untreated) ears. CONCLUSION: XIAP delivery to the cochlea can protect against the audiometric changes and hair-cell loss associated with cisplatin ototoxicity. The efficacy, specificity, and duration of the protective effects make this a potentially attractive therapeutic paradigm.

Animals↗
PubMed2005

Facial nerve rerouting in skull base surgery.

Facial nerve rerouting techniques were developed to facilitate re-section of extensive tumors occupying the skull base. Facial nerve rerouting has its own limitations and risks, requiring microsurgical expertise, additional surgical time, and often some degree of facial nerve paresis. This article presents different degrees of anterior and posterior facial nerve rerouting, techniques of facial nerve rerouting, and a comprehensive review of outcomes. It then reviews anatomic and functional preservation of the facial nerve in acoustic neuroma resection, technical aspects of facial nerve dissection, intracranial facial nerve repair options, and outcomes for successful acoustic neuroma surgery.

Cranial Fossa, Middle↗
PubMed2005

Hyperbaric oxygen therapy for sudden sensorineural hearing loss: a prospective trial of patients failing steroid and antiviral treatment.

OBJECTIVE: To investigate the safety and efficacy of hyperbaric oxygen therapy (HBOT) in adult patients with sudden sensorineural hearing loss (SSNHL) who fail standard of care steroid and antiviral therapy. STUDY DESIGN: Prospective cohort study. SETTING: An urban tertiary referral center. PATIENTS: Nine adult patients presenting with SSNHL from December 2002 through February 2004. Patients with acute onset SSNHL of greater than 30 dB in three contiguous frequencies who failed to show audiometric improvement after 2 weeks of systemic steroids and antivirals were enrolled. INTERVENTIONS: Study patients received HBOT at 2.0 atmospheric pressure for 90 minutes while breathing 100% oxygen under a clear plastic hood in the chamber. Treatments were administered daily for 10 days over a 2-week period. MAIN OUTCOME MEASURES: Pre-and postHBOT mean hearing gains measured in decibels for pure-tone audiometry at 0.5, 1, 2, 3, and 4 KHz for bone and additional 8 KHz for air; pure-tone averages for air and bone; speech reception thresholds; and speech discrimination levels. Patient-reported subjective recovery rates (completely, substantially, partially, not improved) were also recorded. RESULTS: Overall, two patients had a dramatic improvement, and one patient had a dramatic improvement in his speech discrimination without improvement in other audiometric measures. Six patients had no demonstrable hearing gains. Two patients had complications of serous otitis media requiring myringotomy and pressure equalizing tube placement. No other complications were observed. CONCLUSIONS: Secondary HBOT after failure of systemic steroid and antiviral therapy may be associated with hearing gains in some patients with SSNHL.

Adult↗
PubMed2004

Relationship of petrous temporal bone pneumatization to the eustachian tube lumen.

OBJECTIVES/HYPOTHESIS: Objectives were to determine the incidence of petrous apex pneumatization and to define the relationship between a pneumatized petrous temporal bone and the eustachian tube lumen. STUDY DESIGN: Retrospective study with institutional review board approval including only adult patients. METHODS: One hundred head computed tomography (ct) scans and 204 petrous temporal bone CT scans performed at a tertiary teaching hospital were reviewed. The two senior authors (s.h.s., p.c.s.) independently reviewed the petrous temporal bone CT scans for grade of pneumatization. Pneumatized CT scans were then reviewed for the presence of a direct communication with the eustachian tube lumen. Significance was determined using the chi test and Pearson correlation of ranks. RESULTS: The incidence of peritubal cells opening into the eustachian tube anterior to the tympanic orifice was 92%. CONCLUSION: The direct communication of peritubal cells with the bony eustachian tube may play a role in the development of persistent cerebrospinal fluid rhinorrhea after cerebellopontine angle surgery.

Adult↗
PubMed2004

The incidence of cerebrospinal fluid leak after vestibular schwannoma surgery.

OBJECTIVE: To review the incidence of cerebrospinal fluid leak after vestibular schwannoma removal reported in the literature. DATA SOURCES: MEDLINE and PubMed literature search using the terms "acoustic neuroma" or "vestibular schwannoma," and "cerebrospinal fluid leak" or "cerebrospinal fluid fistula" covering the period from 1985 to the present in the English language literature. A review of bibliographies of these studies was also performed. STUDY SELECTION: Criteria for inclusion in this meta-analysis consisted of the availability of extractable data from studies presenting a defined group of patients who had undergone primary vestibular schwannoma removal and for whom the presence and absence of cerebrospinal fluid leakage was reported. Studies reporting combined approaches were excluded. No duplications of patient populations were included. Twenty-five studies met the inclusion criteria. DATA EXTRACTION: Quality of the studies was determined by the design of each study and the ability to combine the data with the results of other studies. All of the studies were biased by their retrospective, nonrandomized nature. DATA SYNTHESIS: Significance (p < 0.05) was determined using the chi2 test. CONCLUSIONS: Cerebrospinal fluid leak occurred in 10.6% of 2,273 retrosigmoid surgeries, 9.5% of 3,118 translabyrinthine surgeries, and 10.6% of 573 middle fossa surgeries. The type of cerebrospinal fluid leak was not associated with surgical approach. Meningitis was significantly associated with cerebrospinal fluid leak (p < 0.05). Age and tumor size were not associated with cerebrospinal fluid leak.

Cerebrospinal Fluid Otorrhea↗
PubMed2004

Management options for cerebrospinal fluid leak after vestibular schwannoma surgery and introduction of an innovative treatment.

OBJECTIVE: To review the management of cerebrospinal fluid leak after vestibular schwannoma removal reported in the literature and to present a novel approach to management of recalcitrant cases. DATA SOURCES: MEDLINE and PubMed literature search using the terms "cerebrospinal fluid leak" or "cerebrospinal fluid fistula" and "acoustic neuroma" or "vestibular schwannoma" covering the period from 1985 to present in English. A review of bibliographies of these studies was also performed. STUDY SELECTION: Criteria for inclusion in this meta-analysis consisted of the availability of extractable data from studies presenting a defined group of patients who had undergone primary vestibular schwannoma removal and for whom the presence and absence of cerebrospinal fluid leakage was reported. Studies reporting combined approaches were excluded. No duplications of patient populations were included. Twenty-five studies met the inclusion criteria. DATA EXTRACTION: Quality of the studies was determined by the design of each study and the ability to combine the data with the results of other studies. All of the studies were biased by their retrospective, nonrandomized nature. DATA SYNTHESIS: Significance (p < 0.05) was determined using the chi test. CONCLUSIONS: Incisional cerebrospinal fluid leakage responded well to local management and lumbar drainage. Rhinorrhea often necessitated surgical intervention. No specific reoperation techniques correlated exclusively with better reoperation outcomes. The transaural/transnasal approach presents an alternative for surgical management of cerebrospinal fluid rhinorrhea.

Adult↗
PubMed2003

Mitomycin-C in the postsurgical ear canal.

OBJECTIVE: Our goal was to evaluate the use of topical mitomycin-C (MMC) in the prevention of scar tissue formation in the postsurgical external auditory canal (EAC). Study design and setting We conducted a prospective pilot study at a tertiary care institution. METHODS: Six patients with recurrent postoperative granulation tissue after canaloplasty, tympanomastoidectomy, or lateral temporal bone resection were included. MMC (0.5 mg/mL) was applied topically for 5 minutes to the EAC/mastoid cavity. RESULTS: Outcomes were measured at initial MMC application and 1 and 3 months thereafter using a visual analog scale score based on the degree of EAC occlusion by granulation tissue. Need for debridement of recurrent granulation tissue on follow-up was noted. Three (50%) patients had improved VAS 1 month after treatment. Two (33%) had improved visual analog scale score at 3 months. Five (83%) required at least one debridement procedure. Repeat MMC application was performed in 2 patients. CONCLUSION: Topical MMC was ineffective in preventing scar formation in the postsurgical EAC.

Adult↗
PubMed2003

The incudostapedial joint angle: implications for stapes surgery prosthesis selection and crimping.

OBJECTIVE: To evaluate the role of the incudostapedial joint (ISJ) angle in stapes prosthesis size selection and crimping. METHODS: The ISJ of 13 cadaveric human temporal bones were photographed, then measured using computer-aided design software. The relationship of ISJ angle to prosthesis length was modeled. A literature review evaluated factors contributing to stapedectomy failure. RESULTS: The mean ISJ angle was 93.0 degrees (SD = 8.3 degrees ) (range, 75.0 degrees -104.0 degrees ). The mean ISJ angle deviation from 90 degrees was 7.35 degrees (SD = 4.45 degrees ) (range, 0.3 degrees -15.0 degrees ). The mean distance along the incus accessible for prosthesis placement was 3.21 mm (SD = 0.55 mm) (range, 2.00-4.00 mm). CONCLUSIONS: Significant deviation of the ISJ angle from 90 degrees was found (P <.0001). The length along the incus accessible for prosthesis placement was sufficient to result in errors in prosthesis size selection and crimping with only small variations in the ISJ angle. Incorrect prosthesis sizing and crimping are frequently associated with stapedectomy failure. Variations in ISJ anatomy should be considered when selecting stapes prostheses lengths and may affect crimping technique.

Culture Techniques↗
PubMed2003

Regional spread of nonneurogenic tumors to the skull base via the facial nerve.

OBJECTIVE: This study examined the clinical and pathologic features of regional spread of nonneurogenic neoplastic disease to the intratemporal segments of the facial nerve. STUDY DESIGN: Retrospective review.SETTING Three tertiary referral centers. PATIENTS: Six patients with neoplastic disease of nonneurogenic origin involving segments of the facial nerve within the temporal bone. INTERVENTIONS: All patients underwent surgery with curative intent. Five patients received adjuvant radiation, and two received adjuvant radiation and chemotherapy. MAIN OUTCOME MEASURES: Histopathology, site of primary tumor, intratemporal location of regional spread along the facial nerve, degree of facial paralysis, and presence of residual disease. RESULTS: Five cases of malignancy were reported: one case of parotid adenoid cystic carcinoma, one case of parotid mucoepidermoid carcinoma, two cases of squamous cell carcinoma of the skin, and one case of an unidentified carcinoma. Perineural spread was histologically found in all cases of malignant disease. In addition, one case of benign pleomorphic adenoma of the parotid gland that circumferentially involved an intratemporal segment of the facial nerve was reported. Facial paralysis was present in five of six (83%) of cases. Four patients had unresectable malignant disease, and two died despite multimodality therapy. CONCLUSIONS: The facial nerve provides a route for the spread of neoplastic disease into the temporal bone, and perineural invasion is an important mechanism of invasion and motility of malignant disease. Nonneurogenic intratemporal tumors of the facial nerve are a rare but significant cause of facial paralysis.

Adult↗
PubMed2002

Cost-effective diagnosis of acoustic neuromas: a philosophical, macroeconomic, and technological decision.

OBJECTIVE: Our goals were to define the most sensitive techniques of acoustic neuroma diagnosis, to examine their relative costs, and to propose diagnostic modality selection given the rarity of acoustic neuroma incidence and given the other costs that society faces in more commonly encountered diseases. METHODS: We conducted a MEDLINE search of the English language from 1966 to 2001 using the following keywords: acoustic neuroma, acoustic tumor, vestibular schwannoma, diagnosis, cost effectiveness, MRI, auditory brainstem response, brainstem audiometric evoked response, incidence, and prevalence. RESULTS: Although magnetic resonance imaging with gadolinium remains the most sensitive diagnostic modality in the discovery of acoustic neuromas, its cost may be prohibitive for some societies. CONCLUSION: Which modality to use in acoustic neuroma diagnosis is just as much a philosophical and macroeconomic question as a technological one. CLINICAL SIGNIFICANCE: The cost of a timely diagnosis of acoustic neuromas must be weighed against using resources for other, more pressing, health concerns.

Audiometry, Evoked Response↗
PubMed2002

Otologic manifestations of Fanconi anemia.

OBJECTIVES: To identify and define the otologic manifestations in patients with Fanconi anemia. DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Sixty-nine patients in all age groups who received a diagnosis of Fanconi anemia with or without otologic presentation. METHODS: Medical records, audiograms, and tympanograms of all patients were reviewed. Data were analyzed and compared with the literature. RESULTS: Of 69 patients with Fanconi anemia, many had morphologic anomalies affecting the structures of the ear and the head and neck. Conductive hearing loss, external auditory canal stenosis, and auricular malformation were among the most common. CONCLUSIONS: Fanconi anemia is a clinically heterogenous disorder. Conductive hearing loss, external auditory canal stenosis, and auricular malformations are the most common otologic presentations but are not present in the majority of patients.

Acoustic Impedance Tests↗