Ophthalmologist (eyes), Otolaryngologist (ear, nose, throat), Surgical Specialist
24 years of experience
Video profile
Accepting new patients
Henry Ford Medical Center at Maplegrove
6777 W Maple Rd
West Bloomfield, MI 48322
(284) 661-6472
Locations and availability (1)

Education ?

Medical School Score Rankings
University of Michigan Medical School (1986)
  • Currently 4 of 4 apples
Top 25%

Awards & Distinctions ?

Awards  
Castle Connolly's Top Doctors™ (2013)

Affiliations ?

Dr. Seidman is affiliated with 8 hospitals.

Hospital Affilations

Score

Rankings

  • Henry Ford Wyandotte Hospital
    Otolaryngology
    2333 Biddle Ave, Wyandotte, MI 48192
    • Currently 4 of 4 crosses
    Top 25%
  • Henry Ford Macomb Hospitals - Warren Campus
    Otolaryngology
    13355 E 10 Mile Rd, Warren, MI 48089
    • Currently 3 of 4 crosses
    Top 50%
  • Detroit Receiving Hospital & University Health Center
    Otolaryngology
    4201 Saint Antoine St, Detroit, MI 48201
    • Currently 3 of 4 crosses
    Top 50%
  • Henry Ford Hospital
    Otolaryngology
    2799 W Grand Blvd, Detroit, MI 48202
    • Currently 3 of 4 crosses
    Top 50%
  • Henry Ford Macomb Hospitals
    Otolaryngology
    15855 19 Mile Rd, Clinton Township, MI 48038
    • Currently 2 of 4 crosses
  • Henry Ford Medical Center at Maplegrove
    6777 W Maple Rd, West Bloomfield, MI 48322
  • Children's Hospital of Michigan
    3901 Beaubien St, Detroit, MI 48201
  • Cottage Hospital
    159 Kercheval Ave, Grosse Pointe Farms, MI 48236
  • Publications & Research

    Dr. Seidman has contributed to 63 publications.
    Title Clinical Practice Guideline: Polysomnography for Sleep-disordered Breathing Prior to Tonsillectomy in Children.
    Date August 2011
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    This guideline provides otolaryngologists with evidence-based recommendations for using polysomnography in assessing children, aged 2 to 18 years, with sleep-disordered breathing and are candidates for tonsillectomy, with or without adenoidectomy. Polysomnography is the electrographic recording of simultaneous physiologic variables during sleep and is currently considered the gold standard for objectively assessing sleep disorders.

    Title Tinnitus: Current Understanding and Contemporary Management.
    Date January 2011
    Journal Current Opinion in Otolaryngology & Head and Neck Surgery
    Excerpt

    Tinnitus is a debilitating condition that affects a broad range of patients. Despite thorough and extensive research, the cause of tinnitus has yet to be determined. Also, there has never been a single intervention identified that can consistently eliminate the symptoms of tinnitus. However, despite our inability to 'cure' tinnitus, there are many medical and behavioral strategies that may result in symptomatic relief. The purpose of this article is to review some of the previous information on tinnitus and to examine the recent research on the etiology and management of this condition.

    Title Direct Electrical Stimulation of Heschl's Gyrus for Tinnitus Treatment.
    Date April 2008
    Journal The Laryngoscope
    Excerpt

    OBJECTIVES/HYPOTHESIS: The purpose of the study was to determine the effect of electrical stimulation of the auditory cortex in patients with tinnitus. STUDY DESIGN: Nonrandomized clinical trial. METHODS: Two patients with debilitating tinnitus refractory to conventional therapies were treated. Patients were evaluated with validated questionnaires and psychoacoustic measures to determine the frequency and pitch of their tinnitus. Tones at these frequencies were then presented to the first patient (RP) under magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) to determine the tonotopic map for these frequencies in Heschl's gyrus. These tonotopic sites were targeted for implant with a quadripolar electrode. In the second patient (MV), only the fMRI tonotopic map was performed. These fMRI results detected an area of increased activity, which was selected as the site for the implanted bipolar electrode. RESULTS: Patient RP (bilateral tinnitus for 2 years) has experienced a sustained reduction to near elimination of tinnitus with intracerebral implanted electrodes, whereas patient MV (unilateral tinnitus for 7 years) had an unsustained reduction in her tinnitus. CONCLUSION: These findings suggest that the perception and annoyance of tinnitus may be modulated or reduced through electrical stimulation of the auditory cortex. These unsustained effects for patient MV may have been influenced by the longstanding nature of her tinnitus or by another reason as yet undetermined.

    Title Anterior Transcanal Tympanoplasty: a Novel Technique to Repair Anterior Perforations.
    Date March 2008
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    OBJECTIVE: To report a novel, minimally invasive technique for anterior tympanic membrane (TM) perforation repair. STUDY DESIGN: A transcanal repair of the anterior TM was performed on 45 patients. METHODS: A total of 689 patients with chronic suppurative otitis media underwent surgical intervention; of these, 45 patients with isolated anterior TM perforations underwent an anterior tympanoplasty. This approach is similar to a transcanal approach for small posterior perforations; an anterior rather than a posterior flap is raised. RESULTS: Perforations ranged from 20 to 50 percent in size. Preoperative air-bone gaps ranged from 5 to 51 dB and averaged 25 dB. Postoperative air-bone gaps ranged from 0 to 33 dB and averaged 14 dB. Of 45 patients, 40 (88%) had closure of their perforations. Data from 1- to 10-year follow-up are provided. CONCLUSIONS: The anterior transcanal tympanoplasty is a minimally invasive technique to repair anterior TM perforations. The procedure is simple and obviates the need for a large postauricular incision.

    Title Auditory Research Involving Antioxidants.
    Date December 2007
    Journal Current Opinion in Otolaryngology & Head and Neck Surgery
    Excerpt

    PURPOSE OF REVIEW: The role of antioxidants in the management of hearing loss has generated considerable interest over the past several years. Research efforts in this field have yielded many new insights into the molecular and cellular nature of several types of hearing impairment, including age-related, noise-induced, and drug-induced hearing loss. The objective of this paper is to highlight some of the important studies published over the past several years that have further contributed to our understanding of the mechanism of antioxidants in attenuating hearing loss. RECENT FINDINGS: There is compelling evidence to suggest that antioxidant therapy is beneficial in attenuating, improving, or reversing the effects of several types of acquired hearing loss. Cellular and subcellular changes resulting from these types of hearing impairment are remarkably similar and seem to have a common putative mechanism of oxidative stress and damage. Recent studies have lent further credibility to the notion that antioxidant therapy can be of considerable benefit in the treatment of hearing loss. The increasing body of literature pertaining to human studies will shed further light into this fascinating area of research. SUMMARY: This review elucidates the role of antioxidants in hearing loss and illustrates the continued evolution of research efforts in this field.

    Title Re: Alexander Th, Davidson Tm. Intranasal Zinc and Anosmia: the Zinc-induced Anosmia Syndrome. Laryngoscope 2006;116:217-220.
    Date October 2006
    Journal The Laryngoscope
    Title Editorial Comment on "hyperbaric Compression in the Guinea Pig with Perilymph Fistula".
    Date January 2006
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Title Resveratrol-induced Apoptotic Death in Human U251 Glioma Cells.
    Date October 2005
    Journal Molecular Cancer Therapeutics
    Excerpt

    Resveratrol (trans-3,4',5-trihydroxystilbene) is a naturally occurring polyphenolic compound highly enriched in grapes, peanuts, red wine, and a variety of food sources. Resveratrol has antiinflammatory and antioxidant properties, and also has potent anticancer properties. Human glioma U251 cells were used to understand the molecular mechanisms by which resveratrol acts as an anticancer agent, since glioma is a particularly difficult cancer to treat and eradicate. Our data show that resveratrol induces dose- and time-dependent death of U251 cells, as measured by lactate dehydrogenase release and internucleosomal DNA fragmentation assays. Resveratrol induces activation of caspase-3 and increases the cleavage of the downstream caspase substrate, poly(ADP-ribose) polymerase. Resveratrol-induced DNA fragmentation can be completely blocked by either a general caspase inhibitor (Z-VAD-FMK) or a selective caspase-3 inhibitor (Z-DEVD-FMK), but not by a selective caspase-1 inhibitor. Resveratrol induces cytochrome c release from mitochondria to the cytoplasm and activation of caspase-9. Resveratrol also increases expression of proapoptotic Bax and its translocation to the mitochondria. Resveratrol inhibits U251 proliferation, as measured by MTS assay [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt], and induces G0/G1 growth arrest, as determined by flow cytometry. The cyclin-dependent kinase inhibitor, olomoucine, prevents cell cycle progression and resveratrol-induced apoptosis. These results suggest that multiple signaling pathways may underlie the apoptotic death of U251 glioma induced by resveratrol, which warrants further exploration as an anticancer agent in human glioma.

    Title Editorial Comment on "hyperbaric Compression in the Guinea Pig with Perilymph Fistula".
    Date September 2005
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Title Is Oxymetazoline Really Safe for Middle Ear Use.
    Date August 2005
    Journal The Laryngoscope
    Title Neural Response Telemetry Results with the Nucleus 24 Contour in a Perimodiolar Position.
    Date August 2005
    Journal Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
    Excerpt

    OBJECTIVE: The purpose of the study was to analyze changes in neural response telemetry using the Cochlear Nucleus 24 Contour before and after stylet removal in a human model. STUDY DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: Twelve patients (23-72 years old) undergoing cochlear implantation, using the Nucleus 24 Contour implant, secondary to congenital and age-related hearing loss. INTERVENTION: Cochlear implantation with Cochlear Nucleus 24 Contour implant. MAIN OUTCOME MEASURE: Neural response telemetry thresholds were recorded initially with the stylet in and then with the stylet out during the implant procedure. RESULTS: Stimulus levels to obtain neural response telemetry threshold after stylet removal were statistically lower after the stylet was removed. CONCLUSION: The Nucleus 24 Contour achieves a perimodiolar position once the stylet is removed, and this leads to reduction in the current required to elicit a threshold neural response telemetry response.

    Title Role of Bcl-2 Family of Proteins in Mediating Apoptotic Death of Pc12 Cells Exposed to Oxygen and Glucose Deprivation.
    Date February 2005
    Journal Neurochemistry International
    Excerpt

    Apoptotic cell death has been observed in many in vivo and in vitro models of ischemia. However, the molecular pathways involved in ischemia-induced apoptosis remain unclear. We have examined the role of Bcl-2 family of proteins in mediating apoptosis of PC12 cells exposed to the conditions of oxygen and glucose deprivation (OGD) or OGD followed by restoration of oxygen and glucose (OGD-restoration, OGD-R). OGD decreased mitochondrial membrane potential and induced necrosis of PC12 cells, which were both prevented by the overexpression of Bcl-2 proteins. OGD-R caused apoptotic cell death, induced cytochrome C release from mitochondria and caspase-3 activation, decreased mitochondrial membrane potential, and increased levels of pro-apoptotic Bax translocated to the mitochondrial membrane, all of which were reversed by overexpression of Bcl-2. These results demonstrate that the cell death induced by OGD and OGD-R in PC12 cells is potentially mediated through the regulation of mitochondrial membrane potential by the Bcl-2 family of proteins. It also reveals the importance of developing therapeutic strategies for maintaining the mitochondrial membrane potential as a possible way of reducing necrotic and apoptotic cell death that occurs following an ischemic insult.

    Title Intratympanic Treatment of Hearing Loss with Novel and Traditional Agents.
    Date February 2005
    Journal Otolaryngologic Clinics of North America
    Excerpt

    As knowledge of the cellular and molecular pathophysiology behind otopathologies expands, the possibility exists of preventing sensorineural hearing loss and perhaps reversing the loss. Cellular and molecular mechanisms seem to be similar in hearing loss secondary to aging, drug ototoxicity, noise, or other mechanisms. A final common pathway may hinge upon apoptosis. It is likely that anti-apoptotic factors will increasingly be realized as an important intervention strategy for sensorineural hearing loss. Furthermore, it is also possible that mounting a staged attack at the various regions in the pathway leading to cellular damage using a combination of several protective substances such as steroids, antioxidants, neurotrophic factors, anti-apoptotic compounds, and mitochondrial enhancers may prevent hearing loss and even reverse it in some situations. This article has presented some of the molecular and cellular mechanisms for hearing loss and potential ways of treating them. In theory, the delivery of these medications to the inner ear transtympanically would decrease systemic side effects and be more target specific. Because most of the studies conducted to date have been animal studies, randomized, double-blind, placebo-controlled clinical trials would be necessary before the use of these therapies becomes common practice.

    Title Age-related Hearing Loss and Its Association with Reactive Oxygen Species and Mitochondrial Dna Damage.
    Date December 2004
    Journal Acta Oto-laryngologica. Supplementum
    Excerpt

    Age-related hearing loss, known as presbyacusis, is characterized by the progressive deterioration of auditory sensitivity associated with the aging process and is the leading cause of adult auditory deficiency in the USA. Presbyacusis is described as a progressive, bilateral, high-frequency hearing loss that is manifested on audiometric assessment by a moderately sloping pure tone audiogram. Approximately 23% of the population between 65 and 75 years of age, and 40% of the population older than 75 years of age are affected by this condition. It was estimated in 1980 that 11% of the population was 76 years or older and this number is expected to almost double by the year 2030. When one considers that the population over 65 years of age is experiencing the most accelerated development of hearing loss, the potential socioeconomic ramifications are staggering. Curiously, the frequency of presbyacusis varies across different societies. This discrepancy has been attributed to many factors including genetics, diet, socioeconomic factors, and environmental variables. The purpose of this article is to review the various molecular mechanisms underlying presbyacusis and to offer insights into potential methods of mitigating the effects of aging on hearing impairment.

    Title A New Approach for Malleus/incus Fixation: No Prosthesis Necessary.
    Date November 2004
    Journal Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
    Excerpt

    OBJECTIVE: To describe a novel approach to manage malleus/incus fixation. STUDY DESIGN: Retrospective review of 363 patients with conductive hearing loss operated on since 1996. SETTING: Academic tertiary referral center. PATIENTS: Three hundred sixty-three patients with conductive hearing loss, an intact tympanic membrane, and without history for chronic infection underwent middle ear exploration. Three hundred forty-three had otosclerosis and underwent laser stapedotomy; the remaining 20 patients had laser release of their malleus/incus fixation. INTERVENTION: Twenty patients are presented in this paper. Nineteen patients were diagnosed with malleus fixation before surgery. One patient had a total perforation and mobility of the ossicular chain was not verified preoperatively. This patient was, intraoperatively, noted to have complete ossicular fixation. Conductive hearing loss was identified using audiometry and tuning forks. Nineteen of the 20 patients had the diagnosis confirmed using micropneumotoscopy and noting immobility of the malleus. A transcanal approach was used, and the malleus/incus fixation was released using a laser. This space was expanded upon using a drill. A 1.5-2.0 mm space was created where the ossicular fixation existed, thereby reducing the likelihood of refixation. MAIN OUTCOME MEASURE: Audiometric studies before and after intervention were compared. One to seven years of follow up are provided. RESULTS: Preoperative air-bone gaps ranged from 18 dB to 51 dB and averaged 33 dB. Postoperative air-bone gaps ranged from 1-36 dB and averaged 13 dB. No patients have experienced refixation. There were two complications: one perforation requiring a tympanoplasty and one patient sustaining a 20 dB high-frequency sensorineural loss, most likely secondary to inadvertent drill contact to the ossicular chain. CONCLUSION: When fixation of the malleus and/or incus is found, treatment options exist. A common technique involves removal of the incus and head of the malleus and reconstruction with an incus interposition or a partial ossicular prosthesis. Another technique proposed by the senior author (M.D.S.) is maintenance of the normal anatomy and use of the potassium-titanyl-phosphate laser and drill to free the ossicles and widen the epitympanum. This series shows successful closure of the air-bone gap with this technique.

    Title Ossicular Reconstruction Using Bone Cement.
    Date July 2004
    Journal Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
    Excerpt

    OBJECTIVE: The objective of this study was to describe our results of ossicular reconstruction using bone cement. STUDY DESIGN: We conducted a retrospective review of 264 patients with chronic suppurative otitis media operated on since 1999. SETTING: Academic tertiary referral center. PATIENTS:: Two hundred sixty-four patients with chronic suppurative otitis media underwent mastoidectomy with tympanoplasty. Eighty patients had incudostapedial disarticulation secondary to infection and or cholesteatoma and were reconstructed using an incus interposition graft (n = 31), a partial ossicular prosthesis (POP; n = 31), or more recently, bone source (n = 18). This study evaluates the results of the ossiculoplasties using bone source. INTERVENTION: Ossicular discontinuity was repaired using bone cement. MAIN OUTCOME MEASURE: Audiometric studies pre- and postintervention were compared. One to 3 years of follow up are provided. RESULTS: Preoperative air-bone gaps ranged from 18 dB to 60 dB and averaged 33 dB. Postoperative air-bone gaps ranged from 1 to 24 dB and averaged 10 dB. No patients have experienced any increase in their persistent conductive hearing loss. The pre-/postoperative hearing loss comparisons showed statistically significant hearing improvement. There were no complications. CONCLUSION: The use of POPs and incus interposition grafts is fraught with the possibility of migration and resultant recurrent conductive hearing loss. Using bone cement to reconstruct the ossicular chain restores the integrity of the ossicular chain in the most natural of ways. This reconstruction technique provides an excellent alternative to currently accepted methods and should be considered for incus-stapes disarticulation. There has been no dissolution of the bone source and the results have persisted thus far.

    Title The Effects of Leupeptin on Cochlear Blood Flow, Auditory Sensitivity, and Histology.
    Date April 2004
    Journal The International Tinnitus Journal
    Excerpt

    The purpose of this study was to evaluate the long-term safety of administering leupeptin (1 mg/ml in Hank's Balanced Salt Solution) to the round window membrane by investigating its effects on cochlear blood flow, auditory sensitivity (i.e., auditory brainstem response), and cochlear histology. A comparison of baseline and posttreatment measurements of cochlear blood flow and mean arterial blood pressure in guinea pigs revealed no significant changes. Auditory brainstem response measurements revealed no significant changes in auditory threshold shifts when compared to controls at the 2-, 4-, 6-, and 8-week time points. Furthermore, poststudy surface preparations of the organs of Corti and cytocochleograms from leupeptin-treated ears and controls revealed no significant hair cell losses. These data suggest that the prolonged administration of leupeptin (1 mg/ml at a rate of 0.5 microliter/hr for 8 weeks) to the round window membrane is not ototoxic. This study may serve as a basis for future clinical trials of leupeptin administration for the prevention or treatment of noise-induced hearing loss and the management of tinnitus.

    Title Effect of Sod1 Overexpression on Age- and Noise-related Hearing Loss.
    Date January 2004
    Journal Free Radical Biology & Medicine
    Excerpt

    Reactive oxygen species (ROS) have been implicated in hearing loss associated with aging and noise exposure. Superoxide dismutases (SODs) form a first line of defense against damage mediated by the superoxide anion, the most common ROS. Absence of Cu/Zn SOD (SOD1) has been shown to potentiate hearing loss related to noise exposure and age. Conversely, overexpression of SOD1 may be hypothesized to afford a protection from age- and noise-related hearing loss. This hypothesis may be tested using a transgenic mouse model carrying the human SOD1 gene. Contrary to expectations, here, we report that no protection against age-related hearing loss was observed in mice up to 7 months of age or from noise-induced hearing loss when 8 week old mice were exposed to broadband noise (4-45 kHz, 110 dB for 1 h). Mitochondrial DNA deletion, an index of aging, was elevated in the acoustic nerve of transgenic mice compared to nontransgenic littermates. The results indicate the complexity of oxidative metabolism in the cochlea is greater than previously hypothesized.

    Title Alternative Medications and Other Treatments for Tinnitus: Facts from Fiction.
    Date August 2003
    Journal Otolaryngologic Clinics of North America
    Excerpt

    Tinnitus is a significant medical problem affecting approximately 50 million Americans, 12 million of them severely. Once a thorough evaluation has been performed by a qualified otolaryngologist, and no life-threatening pathology has been identified, the opportunity for treatment exists. Treatment options are extensive and range from approved protocols to anecdotal remedies. Although tinnitus may not miraculously disappear, many therapeutic options exist that may help to make the tinnitus more manageable.

    Title Pharmacologic Manipulation of the Labyrinth with Novel and Traditional Agents Delivered to the Inner Ear.
    Date June 2003
    Journal Ear, Nose, & Throat Journal
    Excerpt

    We describe the methodology and rationale behind the delivery of therapeutic medicines to the inner ear. The inner ear has long been impervious to pharmacologic manipulation. This is most likely the result of a protective mechanism called the blood-labyrinth barrier, whose function closely resembles that of the blood-brain barrier. This protective barrier impedes the clinician's ability to treat inner ear diseases with systemically administered medications. Since 1935, otolaryngologists have attempted to manipulate the inner ear with trans-tympanically injected medicines. Success has varied widely, but medicinal ablation of vestibular function can be achieved in this manner. Unfortunately, the auditory system is also at great risk from any medicine that is delivered to the inner ear via the middle ear. Over the past 10 years, significant improvements in drug delivery have allowed for more "titratable" treatment, which has reduced (but not eliminated) the risk of permanent hearing loss. In this article, we discuss both novel and time-tested methods of delivering medicines to the inner ear. We also review the classes of medications that alter inner ear function and the attendant risks of such treatments.

    Title Re: Myths in Neurotology, Revisited: Smoke and Mirrors in Tinnitus Therapy.
    Date March 2003
    Journal Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
    Title Influence of Lecithin on Mitochondrial Dna and Age-related Hearing Loss.
    Date October 2002
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    OBJECTIVES: Lecithin is a polyunsaturated phosphatidylcholine (PPC), which are high energy functional and structural elements of all biologic membranes. PPC play a rate-limiting role in the activation of numerous membrane-located enzymes, including superoxide dismutase and glutathione, which are important antioxidants protecting cell membranes from damage by reactive oxygen species (ROS). ROS-induced damage to mitochondrial DNA may lead to reduced mitochondrial function in the cochlea and resultant hearing loss. STUDY DESIGN AND SETTING: The effects of lecithin on aging and age-associated hearing loss were studied in rats by measuring hearing sensitivities using auditory brainstem responses (ABR). In addition, mitochondrial function as a measure of aging was assessed by determining mitochondrial membrane potentials using flow cytometry and by amplifying mitochondrial DNA deletions associated with aging. Harlan-Fischer rats aged 18 to 20 months (n = 14) were divided into 2 groups. The experimental group was supplemented orally for 6 months with lecithin, a purified extract of soybean phospholipid (Nutritional Therapeutics, Allendale, NJ). RESULTS: The data obtained were compared with the control group. ABRs were recorded at 2-month intervals and showed significant preservation of hearing sensitivities in the treated subjects. Flow cytometry revealed significantly higher mitochondrial membrane potentials in the treated subjects, suggesting preserved mitochondrial function. Finally, the common aging mitochondrial DNA deletion (mtDNA(4834)) were amplified from brain and cochlear tissue including stria vascularis and auditory nerve. This specific deletion was found significantly less frequent in all tissues in the treated group compared with the controls. CONCLUSION: These experiments support our hypothesis and provide evidence that lecithin may preserve cochlear mitochondrial function and protect hearing loss associated with aging.

    Title Molecular Mechanisms of Age-related Hearing Loss.
    Date September 2002
    Journal Ageing Research Reviews
    Excerpt

    Age-related hearing loss, known as presbyacusis, is characterized by the progressive deterioration of auditory sensitivity associated with aging and is the most common cause of adult auditory deficiency in the United States. Presbyacusis is defined as a progressive, bilateral, high-frequency hearing loss that is manifested on audiometric assessment by a moderately sloping pure tone audiogram. This condition affects approximately 23% of the population between 65 and 75 years of age and 40% of the population older than 75 years of age. In 1980, it was estimated that 11% of the population was 76 years or older and this number is expected to nearly double by the year 2030 [, Otolaryngol. Head Neck Surg. 100, 262]. When coupled with the fact that the population over 65 years of age is experiencing the most rapid progression of hearing loss, the potential socioeconomic ramifications are staggering. Interestingly, presbyacusis varies in its frequency across differing societies. This discrepancy has been attributed to many factors such as genetics, diet, socioeconomic factors, and environmental variables [, Otolaryngol. Head Neck Surg. 100, 266;. Scand. Audiol. 26 (1997) 133]. The purpose of this discussion is to illuminate the various molecular mechanisms underlying this age-related hearing loss and to offer insights into potential ways to mitigate the effects of aging on hearing impairment.

    Title Genetics, the Facial Plastic and Reconstructive Surgeon, and the Future.
    Date December 2001
    Journal Archives of Facial Plastic Surgery : Official Publication for the American Academy of Facial Plastic and Reconstructive Surgery, Inc. and the International Federation of Facial Plastic Surgery Societies
    Excerpt

    Predicting the future is a daunting task that is typically reserved for visionaries or tarot card readers. Nonetheless, the challenge is set, and this brief essay will predict how genetics and molecular biology may affect diseases in facial plastic and reconstructive surgery.

    Title A Specific Mitochondrial Dna Deletion (mtdna4977) is Identified in a Pedigree of a Family with Hearing Loss.
    Date August 2001
    Journal Hearing Research
    Excerpt

    This paper presents a family pedigree of sensorineural hearing loss in patients with a mitochondrial DNA (mtDNA) deletion. Genomic DNA screenings including myo 15 and connexin 26 were normal. MtDNA deletions are associated with many pathophysiologic conditions, including neurological disorders, sensorineural hearing loss, ischemia, cardiomyopathies and aging. Several mitochondrial disorders secondary to mutations or deletions in mtDNA have been identified in association with deafness. The present study describes a pedigree of five individuals with hearing loss who harbor a 4977 bp common aging deletion, in their mtDNA. Chromosomal analysis was normal in all affected individuals. Audiologic and molecular biologic findings of these patients suggest that the common aging deletion of mtDNA may be a predisposing factor in sensorineural hearing loss in this family.

    Title Surgery for Malleus and Incus Fixation.
    Date August 2001
    Journal Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
    Title Effects of Kynurenic Acid As a Glutamate Receptor Antagonist in the Guinea Pig.
    Date October 2000
    Journal European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-rhino-laryngological Societies (eufos) : Affiliated with the German Society for Oto-rhino-laryngology - Head and Neck Surgery
    Excerpt

    Glutamate excitotoxicity is implicated in both the genesis of neural injury and noise-induced hearing loss (NIHL). Acoustic overstimulation may result in excessive synaptic glutamate, resulting in excessive binding to post-synaptic receptors and the initiation of a destructive cascade of cellular events, thus leading to neuronal degeneration and NIHL. The purpose of this study was to determine whether this apparent excitotoxicity can be attenuated by kynurenic acid (KYNA), a broad-spectrum glutamate receptor antagonist, and protect against noise-induced temporary threshold shifts (TTS). Guinea pigs were randomly assigned to three separate groups. Base-line compound action potentials (CAP) thresholds and cochlear microphonics (CM) were recorded. Group I was treated with physiologic saline as a vehicle control applied to the round window membrane that was followed by 110 dB SPL wide-band noise for 90 min. Group II received 5 mM KYNA followed by noise exposure, and group III received 5 mM KYNA alone without noise exposure. Post-drug and noise levels of CAP thresholds and CM were then obtained. Noise exposure in the control group caused a significant temporary threshold shift (TTS) of 30-40 dB across the frequencies tested (from 3 kHz to 18 kHz). Animals that received 5 mM KYNA prior to noise exposure (group II) showed statistically significant protection against noise-induced damage and demonstrated a minimal TTS ranging between 5 and 10 dB at the same frequencies. Animals in group III receiving KYNA without noise exposure showed no change in thresholds. Additionally, cochlear microphonics showed no considerable difference in threshold shifts when controls were compared to KYNA-treated animals. These results show that antagonizing glutamate receptors can attenuate noise-induced TTS, suggesting that glutamate excitotoxicity may play a role in acoustic trauma.

    Title Mechanisms of Alterations in the Microcirculation of the Cochlea.
    Date June 2000
    Journal Annals of the New York Academy of Sciences
    Excerpt

    Labyrinthine function is tightly coupled to proper homeostasis. This includes appropriate blood flow that is under strict autoregulatory control. Perturbations in labyrinthine microcirculation can lead to significant cochlear and vestibular dysfunction. The etiology of many otologic disorders, including sudden sensorineural hearing loss, presbyacusis, noise-induced hearing loss, and certain vestibulopathies, are suspected of being related to alterations in blood flow. Some of the mechanisms responsible for hypoperfusion and possibly ischemia, within the cochlea, are addressed, with emphasis on the possibility that both noise and age contribute to localized low blood-flow states and stasis. This reduction in blood supply to the cochlea is likely, in part, responsible for reduced auditory sensitivity associated with chronic noise exposure and aging.

    Title Effects of Dietary Restriction and Antioxidants on Presbyacusis.
    Date May 2000
    Journal The Laryngoscope
    Excerpt

    OBJECTIVES/HYPOTHESIS: The premise of this study is that the membrane hypothesis of aging, also known as the mitochondrial clock theory of aging, is the basis for presbyacusis. Furthermore, it is proposed that treatment with antioxidants or dietary restriction can attenuate age-related hearing loss. Many studies have demonstrated a reduction in blood flow to specific tissues, including the cochlea, with aging. Hypoperfusion leads to the formation of reactive oxygen metabolites (ROM). ROM are highly toxic molecules that directly affect tissues including inner ear structures. In addition, ROM can damage mitochondrial DNA (mtDNA), resulting in the production of specific mtDNA deletions (mtDNA del4977 [human] or mtDNA del4834 [rat]; also known as the common aging deletion]. Previous corroborating data suggest that the common aging deletion mtDNA4834 may be associated not only with aging but also with presbyacusis, thus further strengthening the basis of the current studies. In this study, experiments provide compelling evidence that long-term treatment with compounds that block or scavenge reactive oxygen metabolites attenuate age-related hearing loss and reduce the impact of associated deleterious changes at the molecular level. STUDY DESIGN: Prospective randomized study. METHODS: One hundred thirty rats were randomly assigned to one of six groups with appropriate controls. Animals were divided into the following treatment arms: group 1, 30% caloric restriction; group 2, vitamin E oversupplementation; group 3, vitamin C over-supplementation; group 4, melatonin treatment; group 5, lazaroid treatment; and group 6, placebo. In addition, 10 animals were used to determine the appropriate caloric restriction. All subjects underwent baseline and every-3-month testing until their health failed (range, 18-28 mo; average, 25 mo). This testing included auditory sensitivity studies using auditory brainstem response (ABR) testing, as well as tissue analysis for mtDNA deletions using molecular biological techniques. At the conclusion of the study, animals underwent a final ABR test and were tested for mtDNA deletions in brain and inner ear tissues, and the opposite ear was used for histological analysis. RESULTS: Results indicated that the 30%-caloric-restricted group maintained the most acute auditory sensitivities, the lowest quantity of mtDNA deletions, and the least amount of outer hair cell loss. The antioxidant-treated subjects had improved auditory sensitivities, and a trend for fewer mtDNA deletions was observed compared with the placebo subjects. The placebo subjects had the poorest auditory sensitivity, the most mtDNA deletions, and the greatest degree of outer hair cell loss. CONCLUSIONS: Intervention designed to reduce reactive oxygen metabolite damage appears to protect against age-related hearing loss specifically and aging in general. This is reflected by an overall reduction in mtDNA deletions. These data also suggest that the common aging deletion appears to be associated with presbyacusis, as demonstrated by an increased frequency of the mtDNA del4834 in the cochleae with the most significant hearing loss. Nutritional and pharmacological strategies may very well provide rational treatment options that would limit the age-associated increase in ROM generation, reduce mtDNA damage, and reduce the degree of hearing loss as the organism advances in age.

    Title Biologic Activity of Mitochondrial Metabolites on Aging and Age-related Hearing Loss.
    Date May 2000
    Journal The American Journal of Otology
    Excerpt

    HYPOTHESIS: Compounds that upregulate mitochondrial function in an aging model will improve hearing and reduce some of the effects of aging. BACKGROUND: Reactive oxygen metabolites (ROM) are known products of oxidative metabolism and are continuously generated in vivo. More than 100 human clinical conditions have been associated with ROM, including atherosclerosis, arthritis, autoimmune diseases, cancers, heart disease, cerebrovascular accidents, and aging. The ROM are extremely reactive and cause extensive DNA, cellular, and tissue damage. Specific deletions within the mitochondrial DNA (mtDNA) occur with increasing frequency in age and presbyacusis. These deletions are the result of chronic exposure to ROM. When enough mtDNA damage accrues, the cell becomes bioenergetically deficient. This mechanism is the basis of the mitochondrial clock theory of aging, also known as the membrane hypothesis of aging. Nutritional compounds have been identified that enhance mitochondrial function and reverse several age-related processes. It is the purpose of this article to describe the effects of two mitochondrial metabolites, alpha-lipoic acid and acetyl L-carnitine, on the preservation of age-related hearing loss. METHODS: Twenty-one Fischer rats, aged 24 months, were divided into three groups: acetyl-l-carnitine, alpha-lipoic acid, and control. The subjects were orally supplemented with either a placebo or one of the two nutritional compounds for 6 weeks. Auditory brainstem response testing was used to obtain baseline and posttreatment hearing thresholds. Cochlear, brain, and skeletal muscle tissues were obtained to assess for mtDNA mutations. RESULTS: The control group demonstrated an expected age-associated threshold deterioration of 3 to 7 dB in the 6-week study. The treated subjects experienced a delay in progression of hearing loss. Acetyl-l-carnitine improved auditory thresholds during the same time period (p<0.05). The mtDNA deletions associated with aging and presbyacusis were reduced in the treated groups in comparison with controls. CONCLUSIONS: These results indicate that in the proposed decline in mitochondrial function with age, senescence may be delayed by treatment with mitochondrial metabolites. Acetyl-l-carnitine and alpha-lipoic acid reduce age-associated deterioration in auditory sensitivity and improve cochlear function. This effect appears to be related to the mitochondrial metabolite ability to protect and repair age-induced cochlear mtDNA damage, thereby upregulating mitochondrial function and improving energy-producing capabilities.

    Title Hot-water Irrigation in the Treatment of Posterior Epistaxis.
    Date November 1999
    Journal Archives of Otolaryngology--head & Neck Surgery
    Title Reactive Oxygen Metabolites, Antioxidants and Head and Neck Cancer.
    Date August 1999
    Journal Head & Neck
    Excerpt

    This manuscript will review the probable role of reactive oxygen metabolites (ROM) in the etiopathogenesis of head and neck cancer (HNC). Cancer is a heterogeneous disorder with multiple etiologies including somatic and germ-line mutations, cellular homeostatic disturbances, and environmental triggers. Certain etiologies are characteristic of HNC and include infectious agents such as the Epstein-Barr virus, the use of tobacco, and consumption of alcohol. A large body of evidence implicates ROM in tumor formation and promotion. ROM species are formed in the process of cellular respiration, specifically during oxidative phosphorylation. These ubiquitous molecules are highly toxic in the cellular environment. Of the many effects of ROM, especially important are their effect on DNA. Specifically, ROM cause a variety of DNA damage, including insertions, point mutations, and deletions. Thus, it is hypothesized that ROM may be critically involved in the etiology of malignant disease through their possible impact on protooncogenes and tumor suppressor genes. Additionally, empirical evidence suggests that ROM may also affect the balance between apoptosis and cellular proliferation. If apoptotic mechanisms are overwhelmed, uncontrolled cellular proliferation may follow, potentially leading to tumor formation. Thus, this manuscript will critically review the evidence that supports the role of ROM in tumorigenesis. ROM scavengers and blockers have shown both in vivo and in vitro effects of attenuating the toxicity of ROM. Such compounds include the antioxidant vitamins (A, C, and E), nutrient trace elements (selenium), enzymes (superoxide dismutase, glutathione peroxidase, and catalase), hormones (melatonin), and a host of natural and synthetic compounds (lazaroids, allopurinol, gingko extract). Thus, this paper will also review the possible benefit derived from the use of such scavengers/blockers in the prevention of HNC.

    Title Ethical Issues for Otolaryngology and Surgery in the Elderly.
    Date July 1999
    Journal Ear, Nose, & Throat Journal
    Excerpt

    Clinical ethics is an intrinsic aspect of medical practice. Concerns for ethical conduct arise in the management of medical benefits, patient preferences, quality of life, and the relationship between patient care and its attendant familial, social, economic, and legal circumstances. Ethical concerns in surgical practice are central to the essence of the Hippocratic doctrine, "First do no harm." In caring for our patients, particularly in light of the modern practice of medicine, we often use the risk-benefit calculus. The range of ethical concerns for the otolaryngologist who deals with the elderly and infirm covers many diverse situations. Superimposed over this spectrum is the idea of patient autonomy, which is considered to be a cardinal issue in any ethical discussion. Furthermore, increasing medical care costs have created a debate regarding the rationing of healthcare. Ethicists continue the discussion as to whether age should be a decisive factor in the rationing of this care. Definitions of "heroic" and "extraordinary" assume greater significance, and controversies of language become pivotal when the comprehension and cognitive orientation of the patient are compromised by disease and senescence.

    Title Palatal Myoclonus As a Cause of Objective Tinnitus: a Report of Six Cases and a Review of the Literature.
    Date June 1999
    Journal Ear, Nose, & Throat Journal
    Excerpt

    We describe 6 new cases of palatal myoclonus (PM), a rare disorder that is characterized by involuntary rhythmic contraction of the palatal musculature. Although it has been reported that PM is a lifelong condition, one of our patients experienced a complete resolution of PM, which casts doubt on the accepted beliefs about the persistence of PM. Included in this report is the first published case of voluntary PM with objective tinnitus.

    Title Effect of Transtympanic Injection of Steroids on Cochlear Blood Flow, Auditory Sensitivity, and Histology in the Guinea Pig.
    Date June 1998
    Journal The American Journal of Otology
    Excerpt

    HYPOTHESIS: Transtympanic application of steroids is not harmful to the inner ear. BACKGROUND: Steroids are routinely used to treat inner ear pathologies, such as sudden sensorineural hearing loss and autoimmune inner ear disease. The transtympanic route has received increased attention as it can lead to higher levels in tissue and nearly eliminate systemic effects. There has been concern over the safety of applying these drugs directly to the inner ear. METHODS: This study investigates the effects of transtympanic Dexamethasone injection on cochlear blood flow using laser Doppler flowmetry, auditory sensitivity using auditory brain stem responses, and histology in the guinea pig. RESULTS: Results show a significant increase in cochlear blood flow within 30 s to a mean of 29.26% without significant change in auditory sensitivity. The increase in cochlear blood flow was sustained and did not return to baseline for at least 1 hour after drug application. No histologic changes were observed. CONCLUSIONS: These results suggest that transtympanic steroid application is not likely to be detrimental to the inner ear. Additionally, the increase in blood flow may indicate a possible mechanism accounting for the pharmacologic effects of steroids in the inner ear.

    Title Sarthran Preserves Cochlear Microcirculation and Reduces Temporary Threshold Shifts After Noise Exposure.
    Date June 1998
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    The cause of noise-induced hearing loss remains unclear despite years of both epidemiologic and experimental investigation. Among the many possible pathophysiologic mechanisms that may contribute to noise-induced temporary or permanent threshold shifts are insufficiencies in cochlear blood flow. Although the literature is inconsistent, several histologic and physiologic studies demonstrate signs of reduced circulation in the cochlea after noise exposure. Recent studies using computer-enhanced intravital microscopy complement these earlier findings. Evidence suggests that these microcirculatory events are mediated in part by several circulating factors, including the potent vasoactive peptide angiotensin. This study investigated this possibility by pretreating with the angiotensin receptor antagonist sarthran during noise exposure and examining both cochlear microcirculation and auditory sensitivity. The results of these experiments show noise-induced ischemia in the lateral wall of the cochlea and temporary threshold shifts. Treatment with sarthran prevented this noise-induced microcirculatory ischemia and preserved auditory sensitivity at the low frequencies tested. These findings support a role for the angiotensinergic system during noise exposure and suggest that preservation of cochlear blood flow is functionally related to auditory sensitivity.

    Title In Vivo Vestibular Blood Flow in the Mongolian Gerbil: Angiotensin Iii-provoked Changes in Systemic and Local Factors.
    Date December 1997
    Journal Acta Oto-laryngologica
    Excerpt

    The current literature contains little information on vestibular end organ blood flow. The absence of an accepted model, difficulties applying dynamic in vivo measurement techniques and the inaccessibility of the inner ear organs contribute to the shortage of experimental findings. The purpose of the current study is to introduce the gerbil as a viable model for the in vivo study of vestibular blood flow dynamics. The potent vasoactive peptide, angiotensin III (AIII), was used to provoke blood pressure and blood flow changes. The results of this study demonstrate that viable blood flow measures may be obtained from the vestibule of the gerbil. Dose-dependent changes in blood pressure and vestibular blood flow were observed in response to high concentrations of AIII. Pretreatment with the receptor antagonist, sarthran, attenuated both blood pressure and blood flow increases in response to subsequent AIII infusions. The gerbil model offers the advantages of easily accessible and identifiable peripheral vestibular organs, as well as responsive local blood flow. Investigations using this model may provide information on the regulation of blood flow during presentation with a variety of stimulus modalities. Information from such studies may lead to development of strategies for treatment of vestibulopathies suspected to be of vascular origins.

    Title Local Effects of Nitric Oxide on Vestibular Blood Flow in the Mongolian Gerbil.
    Date December 1997
    Journal European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-rhino-laryngological Societies (eufos) : Affiliated with the German Society for Oto-rhino-laryngology - Head and Neck Surgery
    Excerpt

    There is a paucity of studies regarding the regulation of vestibular blood flow (VBF), despite the possibility that vascular alterations may contribute to specific vestibulopathies. The current experiments used the Mongolian gerbil as an animal model since it provides easy surgical access to the vestibular end-organs and has been previously used for physiologic studies involving inner ear function. VBF changes were measured in the posterior semicircular canal using laser Doppler flowmetry following round window membrane (RWM) application of the nitric oxide donor 1, 3-propanediamine-N-[4-1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazi no] butyl (spermine NONOate; SPNO) as a vasodilator. The specificity of the responses induced was tested via pretreatment with an NO scavenger, 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazonline-1-oxyl-3-oxide (carboxy-PTIO; cPTIO). cPTIO, SPNO, vehicle (control) or cPTIO/SPNO were applied to the RWM, during which blood pressure and VBF were monitored for baseline, treatment, and recovery conditions. Results showed concentration-dependent increases in flow, probably resulting from NO's vasodilatory action on local vasculature. cPTIO pretreatment was found to attenuate SPNO-induced VBF increases. These findings support a role of NO in maintaining the vestibular microcirculation.

    Title Mitochondrial Dna Deletions Associated with Aging and Presbyacusis.
    Date November 1997
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    BACKGROUND: The membrane hypothesis of aging proposes an association between reactive oxygen metabolites and aging processes. Reactive oxygen metabolites are a normal by-product of oxidative phosphorylation and are also formed under conditions of ischemia, hypoperfusion, and as a result of environmental contaminants. Among the many detrimental activities of reactive oxygen metabolites, also known as free oxygen radicals, is direct damage to mitochondrial DNA. Progressive accumulation of mitochondrial DNA damage renders cells unable to conduct oxidative phosphorylation reactions effectively, thereby leading to a bioenergetically deficient cell. Over time, mitochondrial DNA damage accumulates and leads to cellular dysfunction with subsequent organ failure, aging, and ultimately, death. This sequence forms the basis of the membrane hypothesis of aging. OBJECTIVE: To determine if the membrane hypothesis of aging may be involved in the development of presbyacusis. DESIGN: Fischer rats from 4 age groups were tested for auditory sensitivity using the auditory brainstem response. Brain, stria vascularis, and auditory nerve tissues were harvested and mitochondrial DNA was amplified to identify the highly conserved cytochrome b and ND1-16S ribosomal RNA segment of the NADH genes, as well as a 4834-base pair (bp) deletion associated with aging. SUBJECTS: Fischer rats (n=28) from 4 age groups were used: young (2-4 months [n=9]), mid-young (9-11 months [n=5]), mid-old (18-20 months [n=5]), and old (30-34 months [n=9]). RESULTS: The results demonstrate a progressive reduction in auditory sensitivity with age. The mitochondrial DNA studies identify a significant increase in the presence of the 4834-bp deletion in the aged subjects compared with the young. CONCLUSIONS: These findings raise the possibility that the 4834-bp deletion may be associated with presbyacusis, as well as with aging.

    Title Mitochondrial Dna Deletions Associated with Aging and Possibly Presbycusis: a Human Archival Temporal Bone Study.
    Date October 1997
    Journal The American Journal of Otology
    Excerpt

    HYPOTHESIS: We attempted to determine if the common mitochondrial DNA aging deletion is also associated with presbycusis. BACKGROUND: Presbycusis is the most common cause of deafness in adults in the United States, affecting approximately 40% of the population older than 75 years of age. The ability to identify a gene(s) or a specific genetic deficit(s) associated with presbycusis has significant clinical importance. METHODS: The current study examined mitochondrial DNA (mtDNA) from cochlear sections of 34 human temporal bones: 17 with normal hearing and 17 with presbycusis. DNA was extracted from celloidin-embedded temporal bone sections; and specific oligonucleotide primers were designed to amplify the cytochrome b gene and a 4,977 base pair (bp) deletion of the mtDNA. Polymerase chain reaction (PCR) was used to amplify the base pair products that correspond to targeted gene regions, and sequencing was used to verify the products. RESULTS: Fourteen of the 17 patients with hearing loss showed the 4,977 bp deletion and this deletion was present in only eight of the 17 human specimens with normal audiograms. The cytochrome b gene was amplified from all specimens. CONCLUSIONS: The current study demonstrates the presence of a 4,977 bp deletion in human mitochondrial DNA genome that is associated with aging and with some forms of presbycusis. These results, coupled with previous animal studies, suggest that this 4,977 deletion may be associated with presbycusis.

    Title Pentoxifylline Maintains Cochlear Microcirculation and Attenuates Temporary Threshold Shifts Following Acoustic Overstimulation.
    Date December 1996
    Journal Acta Oto-laryngologica
    Excerpt

    The etiology of noise-induced hearing loss is poorly understood despite years of clinical experience and experimental investigations. One potential mechanism which may contribute to noise-induced temporary threshold shifts (TTS) are vascular pathologies in the microcirculation of the cochlea. Several studies have demonstrated histologic evidence of reduced cochlear blood flow following noise exposure. Recent studies utilizing intravital microscopy (IVM) complement these histologic studies and furthermore demonstrate localized ischemia during noise exposure. The purpose of the current study was to attempt to maintain cochlear blood flow during noise exposure by treating with pentoxifylline, a xanthine derivative which promotes blood flow in capillary beds. The possibility that preserved cochlear microcirculation with pentoxifylline treatment attenuates noise-induced TTS was also examined in this study. The results show treatment with pentoxifylline maintains cochlear microcirculation as assessed by continuous red blood cell movement through capillaries. Pentoxifylline treatment did not prevent vasoconstriction or increased permeability often observed in the cochlear microvasculature during noise. Treatment with this drug reduced noise-induced TTS.

    Title Age-related Differences in Cochlear Microcirculation and Auditory Brain Stem Response.
    Date December 1996
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    OBJECTIVE: To examine possible age-related differences in auditory sensitivity and cochlear vascular properties. DESIGN: This study is designed to provide information regarding cochlear function using physiological and audiological measures. Each animal underwent intravital microscopic evaluation of red blood cell velocity, vessel diameter, and vascular permeability in the second turn of the cochlear lateral wall. Auditory brain stem responses were used to determine hearing sensitivity. SUBJECTS: Four age ranges of male Fischer rats were studied: young, 2 to 4 months (n = 9); mid-young, 9 to 11 months (n = 8); mid-old, 18 to 20 months (n = 6); and old, 30 to 34 months (n = 10). RESULTS: Auditory brain stem response testing showed an age-related decrease in auditory sensitivity. Intravital microscopic analysis showed age-related statistically significant decreases in red blood cell velocity and increased vascular permeability with a trend for reduced capillary diameters. CONCLUSIONS: The process of aging is associated with many biochemical and physiological changes that include decrease in cellular water concentration, ionic changes, and decreased elasticity of cellular membranes. One contributing factor to this process may be altered vascular characteristics, such as reduced flow and vascular plasticity, as well as increased vascular permeability. These age-related changes may result in reductions in oxygen and nutrient delivery, and also waste elimination. Our results suggest that progressive age-associated vascular compromise may be a contributing factor in presbycusis.

    Title Update on Tinnitus.
    Date November 1996
    Journal Otolaryngologic Clinics of North America
    Excerpt

    The study of a disorder such as tinnitus is fraught with difficulties. Tinnitus, like pain, is a subjective symptom. The problem is compounded because several different mechanisms must operate to cause the persistent sensation of tinnitus. Therefore, it is difficult to measure objectively any improvements in the condition. For example, it has been reported previously that sectioning the eighth cranial nerve does not abolish tinnitus in a majority of patients; therefore, central mechanisms must act to preserve the tinnitus. Finally, we know that tinnitus can occur in a host of conditions other than ototoxicity, aging, and noise exposure. Other conditions that may produce tinnitus are migraine headache with auditory aura, temporal lobe seizures, and head injuries. Therefore, it is naive to conceptualize that tinnitus is a disorder with a unitary origin and a unitary "cure".

    Title Association of Mitochondrial Dna Deletions and Cochlear Pathology: a Molecular Biologic Tool.
    Date July 1996
    Journal The Laryngoscope
    Excerpt

    The purpose of these experiments was to develop a method of isolation, amplification, and identification of cochlear mitochondrial DNA (mtDNA) from minute quantities of tissue. Additionally, studies were designed to detect mtDNA deletions (mtDNA del) from the cochlea that previously have been amplified from other organ systems and tissues. MtDNA del have been associated with many pathologies, including neurological disorders, sensorineural hearing loss, ischemia, cardiomyopathies, and aging. DNA was extracted from rat and human tissues, and polymerase chain reaction was used to amplify mtDNA sequences. A 360 base pair (bp) cytochrome-b gene product and the highly conserved ND1-16S ribosomal ribonucleic acid regions found only in mtDNA were amplified from all tissues. Preliminary studies have identified a 4834 bp mtDNA del in aged rats and a corresponding 4977 bp mtDNA del in aged humans. Additionally, preliminary results in human archival temporal bone studies reveal the presence of the 4977-bp mtDNA deletion in two out of three patients with presbycusis. The deletion was not evident in age-matched control patients without a history of presbycusis. This technique of mtDNA identification makes it possible to investigate specific mtDNA defects from a single cochlea, promoting the study of hereditary hearing loss and presbycusis at a molecular biologic level.

    Title Cochlear Vascular Changes in Response to Loud Noise.
    Date March 1996
    Journal The American Journal of Otology
    Excerpt

    The findings of several authors suggest that alterations in cochlear vascular physiology may contribute to noise-induced hearing loss. Although the influence of noise on cochlear microcirculation is controversial, recent investigations have identified a number of microvascular alterations during noise exposure. Researchers, using intravital microscopy, a technique which offers the advantage of continuous in vivo observation of cochlear lateral wall vessels, have observed alterations in red blood cell velocity and capillary vasoconstriction within the cochlea during exposure to noise. These alterations were sufficient to induce localized periods of stasis, alterations in vascular permeability, and local ischemia. It is possible that such noise-induced vascular ischemia may result in reduced auditory sensitivity.

    Title Distortion-product Otoacoustic Emissions.
    Date April 1995
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Title Lipid Peroxidation Inhibitor Attenuates Noise-induced Temporary Threshold Shifts.
    Date August 1994
    Journal Hearing Research
    Excerpt

    The purpose of this study was to investigate the protective effects of U74389F (Upjohn Co. Kalamazoo, MI), a 21-aminosteroid/lipid peroxidation inhibitor, and a member of the lazaroid drug class, on temporary threshold shifts in animals exposed to prolonged noise stimulation. Animals treated with U74389F and exposed to noise showed attenuated cochlear action potential threshold (CAP) shifts and cochlear microphonic (CM) when compared to non-drug treated noise-exposed subjects. These data suggest that inhibition of FOR induced lipid peroxidation is an important mechanism in noise-induced asymptotic temporary threshold shifts.

    Title Prediction of Facial Nerve Function Following Acoustic Neuroma Resection Using Intraoperative Facial Nerve Stimulation.
    Date June 1994
    Journal The Laryngoscope
    Excerpt

    Methods of monitoring the facial nerve during posterior fossa surgery continue to evolve. In an effort to predict acute and final facial nerve function following acoustic neuroma resection, the lowest current applied to the facial nerve at the brainstem necessary to elicit facial muscle response was measured using strain gauge and electromyographic facial nerve monitors. A retrospective analysis of 121 patients who had undergone acoustic neuroma surgery was performed. Sixty-five patients had intraoperative facial nerve monitoring and 44 had sufficient data for inclusion in this study. The acute and final facial nerve functions, according to the House-Brackmann classification, were assessed with regard to intraoperative stimulation-current thresholds. Nineteen of 20 patients who required 0.10 mA or less to elicit a facial muscle response had a House-Brackmann grade I facial nerve outcome. The upper limit of the 95% confidence interval of stimulation threshold for patients with a final grade I facial nerve function is 0.17 mA. All of the patients in this study, with stimulation thresholds ranging up to 0.84 mA, had a final grade III or better result. A poor outcome in our series, a final grade III facial nerve function, is best predicted by a poor acute result, specifically an acute grade VIA facial nerve function. We suggest that it is possible to predict the facial nerve function based on intraoperative threshold testing.

    Title Substance P Increases Cochlear Blood Flow Without Changing Cochlear Electrophysiology in Rats.
    Date March 1994
    Journal Hearing Research
    Excerpt

    Carotid artery infusions of substance P yielded reductions in systemic blood pressure and elevations in cochlear blood flow (CoBF), measured via laser Doppler flowmeter, with no alterations in cochlear action potentials or cochlear microphonics in Wistar-Kyoto rats. Additionally, direct micro-infusions of substance P into the anterior inferior cerebellar artery, which contributes to the local vascular perfusion of the cochlea, yielded elevations in CoBF with no changes in systemic blood pressure. Pretreatment with a specific substance P receptor antagonist, ([D-Pro2,D-Trp7,9]SP) via the carotid artery or the anterior inferior cerebellar artery, diminished subsequent substance P-induced vascular responses. These results suggest that endogenous substance P, like other vasoactive peptides, may interact with a substance P-specific receptor population in the cochlea and may therefore participate in the ongoing regulation of CoBF. These findings also support the premise that vasodilatory hormones, along with vasoconstrictive agents, may be involved in the autoregulation of CoBF.

    Title Influence of Calcitonin-gene Related Peptide on Cochlear Blood Flow and Electrophysiology.
    Date March 1994
    Journal The American Journal of Otology
    Excerpt

    Intra-arterially infused calcitonin gene-related peptide (CGRP) induced dose-dependent decreases in both systemic blood pressure and cochlear blood flow (CBF). However, when subjects were pretreated systemically or locally with the specific receptor antagonist CGRP(8-37), CBF increased, despite decreases in systemic blood pressure in response to CGRP infusions. Micro-infusions of CGRP directly into the supplying arterial network of the cochlea induced dose-dependent increases in CBF that were blocked by CGRP(8-37) pretreatment. Cochlear electrophysiology, as assessed by cochlear action potential and cochlear microphonics, remained unchanged following each condition tested. These results indicate that CGRP is involved in systemic regulation of blood pressure and contributes to the regulation of CBF.

    Title Intraoperative Facial Nerve Monitoring in Acoustic Neuroma Surgery.
    Date March 1994
    Journal The American Journal of Otology
    Excerpt

    Intraoperative facial nerve monitoring simultaneously using electromyography and mechanical pressure sensors is being used in retrosigmoid and translabyrinthine approaches for acoustic neuroma resection. Insulated electrified microsurgical instruments and air drills are used to stimulate the facial nerve with a pulsed, constant current through bone and tumor, before the facial nerve is visually encountered. Electrical stimulation is used to help locate the facial nerve, map the course of the facial nerve within tumor, warn the surgeon of unexpected facial nerve locations, and help predict facial nerve function postoperatively. In 57 unmonitored cases a House-Brackmann (H-B) grade I or II result was obtained in 77 percent of small, 81 percent of medium, and 60 percent of large tumors. In 64 monitored cases H-B grade I or II was obtained in 88 percent of small, 79 percent of medium, and 90 percent of large tumors. Overall, facial nerve outcomes were better after monitored procedures (p < 0.02). A modified H-B classification for acute facial nerve injury is introduced to grade facial weakness immediately postoperatively and until function is stable at 1 year. In the unmonitored group there were five (9%) cases with a complete facial paralysis, facial nerve intact (i.e., acute H-B grade VIA) and seven (13%) cases with the facial nerve transected (i.e., acute H-B grade VIB). In the monitored group there were five (8%) acute H-B grade VIA and two (3%) acute H-B grade VIB results. In the unmonitored group of large tumors, there were statistically more patients with an acute H-B grade VIB result (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

    Title The Protective Effects of Allopurinol and Superoxide Dismutase on Noise-induced Cochlear Damage.
    Date January 1994
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    Several studies have demonstrated that noise exposure may result in local vasoconstriction of cochlear vessels. The subsequent decrease in cochlear blood flow may lead to hypoxia and predispose to the formation of free oxygen radicals (FORs). If hypoxia occurs in response to noise exposure, then drugs that scavenge or block the formation of FORs should protect the cochlea from damage resulting from hypoxic or ischemic events as well as noise trauma. Rats were exposed to 60 hours of continuous broad-band noise (90 dB SPL) and treated with superoxide dismutase-polyethylene glycol (SOD-PEG), allopurinol, or a control vehicle. Exposure to noise resulted in significant threshold shifts at each frequency tested (3, 8, 12, and 18 kHz) as measured by tone burst-evoked compound action potentials and cochlear microphonics recorded from the round window. Both of these thresholds in drug-treated animals were attenuated compared with animals exposed to noise alone. These findings show that SOD-PEG and allopurinol may preserve cochlear sensitivity associated with noise exposure. This suggests that noise-induced damage to the cochlea may be related to the activity of FORs.

    Title An Algorithm for the Management of Acoustic Neuromas Regarding Age, Hearing, Tumor Size, and Symptoms.
    Date March 1993
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    An algorithm has evolved for the management of patients with acoustic neuroma. Decisions as to surgery vs. observation, surgical approach, and whether hearing preservation should be attempted depend on age, patient symptoms, size of the tumor, residual hearing, and degree of facial nerve involvement at the time of surgery. Conservative management is used for patients over 65 years of age. This consists of observation or subtotal resection through a translabyrinthine approach, depending on the absence or presence of brainstem signs or symptoms. In patients under 65 years of age, hearing preservation is attempted through the retrosigmoid approach in tumors 1.5 cm or less if pure-tone average is less than 30 dB and the discrimination score is greater than 70%. The translabyrinthine approach is our preferred approach for tumors of any size when hearing is not serviceable. A near-total excision is performed when the facial nerve cannot be separated from the tumor. The rationale for this algorithm in the management of 130 cases of acoustic neuroma over the past 17 years is presented.

    Title The Anterior Inferior Cerebellar Arterial Network Supplying the Rat Cochlea and Its Role in Autoregulation of Cochlear Blood Flow.
    Date December 1992
    Journal European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-rhino-laryngological Societies (eufos) : Affiliated with the German Society for Oto-rhino-laryngology - Head and Neck Surgery
    Excerpt

    The sensitivity of the cochlea is dependent upon maintenance of a delicate homeostatic environment. One mechanism which participates in providing this environment is the autoregulation of cochlear blood flow. This autoregulation is ensured through the interaction of sympathetic, peptidergic and hemodynamic mechanisms. The current study demonstrates an adaptation that also participates in cochlear blood flow autoregulation. Specifically, an anterior inferior cerebellar arterial network is described and the relative contributions of each of its vessels to total cochlear blood flow is measured using laser Doppler flowmetry. The results show that each collateral vessel contributes to the blood supply of the cochlea and that reperfusion is accompanied by hyperemia. These findings suggest an adaptation that provides stable blood flow through redundancy and compensatory potential. Additionally, these observations have implications for experimental models of ischemia.

    Title The Protective Effects of Tirilated Mesylate (u74006f) on Ischemic and Reperfusion-induced Cochlear Damage.
    Date February 1992
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    We have recently demonstrated that allopurinol, a blocker of free oxygen radical (FOR) production, and superoxide dismutase (SOD), a scavenger of FOR, protect the cochlea from damage associated with ischemia/reperfusion. The purpose of this present study was to determine if tirilated mesylate (U74006F), a potent inhibitor of lipid peroxidation, can also protect the cochlea from ischemia/reperfusion. Eleven Wistar-Kyoto rats were randomly assigned to two groups: (1) a control group (6 animals) that was exposed to 15 minutes of cochlear ischemia by clamping the anterior-inferior cerebellar artery (AICA), followed by 15 minutes of reperfusion, and (2) a drug-treated group (5 animals) that received U74006F before ischemia/reperfusion. In the control group, the tone burst-evoked compound action potential (CAP) recorded from the round window (RW) was abolished and cochlear microphonic (CM) was reduced. In contrast, the U74006F-treated animals showed post-reperfusion sensitivity in CAP, and less of a CM threshold shift. We interpret these results to indicate that U74006F lessens cochlear damage occurring as a result of ischemia/reperfusion and supports the hypothesis that FOR-induced lipid peroxidation may be partly responsible for the cochlear damage that occurs from ischemia.

    Title Creation of a Lobule: a Simple Technique.
    Date January 1992
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Title The Protective Effects of Allopurinol and Superoxide Dismutase-polyethylene Glycol on Ischemic and Reperfusion-induced Cochlear Damage.
    Date November 1991
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    The purpose of this study was to assess the protective effects of allopurinol, a blocker of free oxygen radical (FOR) formation, and superoxide dismutase-polyethylene glycol (SOD-PEG), a scavenger of FORs, on ischemic and reperfusion-induced cochlear damage. Fifteen Wistar Kyoto rats (WKY) were randomly assigned to three groups: (1) a control group (5 animals) that was exposed to 15 minutes of cochlear ischemia by clamping the anterior inferior cerebellar artery (AICA), followed by 15 minutes of reperfusion as documented by laser Doppler flowmetry; (2) a drug-treated group (5 animals) that received allopurinol before ischemia/reperfusion; and (3) a drug-treated group (5 animals) that received SOD-PEG before ischemia/reperfusion. In the control group, the tone burst-evoked compound action potential (CAP) recorded from the round window (RW) of the cochlea was abolished, and the cochlear microphonic (CM) was reduced after ischemia. In contrast, both allopurinol and SOD-PEG-treated animals showed post-reperfusion sensitivity in CAP and CM measures. We interpret these results to indicate that damage to the cochlear from ischemia and subsequent reperfusion can be attenuated by pretreatment with allopurinol or SOD-PEG. This provides indirect evidence that FORs may be partially responsible for cochlear damage resulting from ischemic conditions.

    Title Angioedema Related to Angiotensin-converting Enzyme Inhibitors.
    Date August 1990
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    Angioedema is a disorder characterized by well-demarcated nonpitting edema involving the tongue, floor of the mouth, larynx, lips, and face. This condition can progress to upper airway obstruction and death. Angiotensin-converting enzyme inhibitors (ACEIs), relatively new antihypertensive agents, act by blocking the formation of angiotensin II, a potent vasoconstrictor and stimulator of aldosterone formation. ACEIs also retard the breakdown of bradykinin, a potent vasodilator, which may lead to the edema seen in nonhereditary angioedema. These ACEIs include enalapril, captopril, lisinopril, saralasin acetate, and a combination of ACEI with diuretics (for example, Capozide). From August 1987 to January 1989, we treated six patients with a nonhereditary form of angioedema related to ingestion of angiotensin-converting enzyme inhibitors. Symptoms developed in all patients within 12 hours after their initial dose of an ACEI. They presented with shortness of breath and dysphagia associated with tongue and floor of the mouth edema. Two of the six required intubation and monitoring in the surgical intensive care unit for 36 to 48 hours. Three required supportive treatment and observation in an intermediate care unit, and one received supportive care in the clinic and was discharged the same day. Specifically, treatment consisted of cessation of inciting agent, steroids, antihistamines, and epinephrine, if not otherwise contraindicated. Assays of C1 esterase inhibitor levels and C4 were normal in all six patients; this was important in order to rule out hereditary forms of angioedema. These cases will be discussed, including a review of the literature, methods of diagnosis, pathophysiology, and treatment of angioedema.

    Title Extracranial Skull Base Chondrosarcoma.
    Date January 1990
    Journal Ear, Nose, & Throat Journal
    Excerpt

    Chondrosarcoma of the skull base is a rare neoplasm. The most common presenting symptoms are hoarseness, dysphagia, and diplopia, which is associated with palsies of cranial nerves X, IX, and VI. The temporal bone is the most common site of tumor origin, followed by the sphenoid bone. These tumors must be differentiated from chordoma, chondroid chordoma, osteogenic sarcoma, enchondroma, and meningioma. Diagnosis is made by patient history, radiologic imaging, and biopsy. The treatment is surgical excision followed by radiation therapy. Five-year survival rates for grades I, II, and III are 90, 81, and 43%, respectively.

    Title Can a Persistent Stapedial Artery Be Safely and Effectively Removed? A Case Report with Therapeutic Implications.
    Date
    Journal The International Tinnitus Journal
    Excerpt

    In the past, a persistent stapedial artery was frequently cited as a reason to discontinue stapes surgery, however, several authors have had success operating on the oval window despite the presence of a persistent artery. We present a case of a patient with conductive hearing loss and tinnitus successfully treated with removal of a persistent stapedial artery that was filling the obturator foramen. This experience, in conjunction with a review of the literature and a discussion with several neurotologic colleagues, leads us to suggest that a stapedial artery can be safely removed allowing unhindered access to the oval window.

    Title Glutamate Antagonists, Steroids, and Antioxidants As Therapeutic Options for Hearing Loss and Tinnitus and the Use of an Inner Ear Drug Delivery System.
    Date
    Journal The International Tinnitus Journal
    Excerpt

    A wealth of anecdotal, empirica], and double-blind placebo-controlled data exists on medicines that may have a beneficial role in the management of patients with tinnitus. Tinnitus is a symptom that affects between 40 and 45 million Americans alone; this represents approximately 14% of the US population. Data exist for Japan (population: 125,732,794), Europe (population: 503 million), and Australia (population: 18,426,900), and estimates suggest that tinnitus affects a similar percentage of those populations (B. Tabachnick, personal communication, 1998). Thus, in those industrialized nations, approximately 90 million may experience tinnitus to some degree. One to two percent of the population expriences debilitating tinnitus, severely limiting the quality of life of affected individuals. All too often, the response from well-trained medical professionals is, "Learn to live with it" or "There is no cure." Although the author does not dispute that currently no cure exists, I contend that help is available. This article discusses the use of glutamate antagonists, steroids, and antioxidants for the management of hearing loss and tinnitus. Additionally, the results of using an inner ear drug delivery system on nine patients with a variety of inner ear disorders are reviewed briefly.

    Title The Jugular Dural Fold-a Helpful Skull Base Landmark to the Cranial Nerves.
    Date
    Journal Skull Base Surgery
    Excerpt

    During a retrosigmoid (or combined retrolabyrinthine-retrosigmoid) approach to the posterior fossa for vestibular neurectomy or removal of small acoustic neuromas, a white dural fold is a consistent landmark to cranial nerves VII through XII. This fold of dura appears as a white linear structure extending from the foramen magnum across the sigmoid sinus, attaching to the posterior aspect of the temporal bone, anterior to the vestibular aqueduct. The name "jugular dural fold" is suggested for this landmark. The jugular dural fold overlies the junction of the sigmoid sinus and the jugular foramen. As measured in formalin-fixed cadaver heads, the overall length of the jugular dural fold is 20.8 mm (+/- 2.9 mm). The cochleovestibular nerve lies 9.9 mm (+/- 1.5 mm) anterior to the superior aspect of the jugular dural fold, the glossopharyngeal nerve lies 9.5 mm (+/- 1.6 mm) anterior to the midpoint of the jugular dural fold, and the operculum of the vestibular aqueduct lies 6.6 mm (+/- 0.7 mm) posterior to the jugular dural fold. Intraoperative measurements in patients undergoing combined retrolabyrinthine-retrosigmoid vestibular neurectomy show an overall length of the jugular dural fold of 16.3 mm (+/- 1.9 mm). The cochleovestibular nerve lies 8.6 mm (+/- 1.3 mm) anterior to the superior aspect of the jugular dural fold, the glossopharyngeal nerve lies 8.6 mm (+/- 1.3 mm) anterior to the midpoint of the jugular dural fold, and the operculum lies 7.5 mm (+/- 0.8 mm) posterior to the jugular dural fold. The jugular dural fold can be used as a reliable landmark for rapidly locating cranial nerves in the posterior fossa.

    Title Noise and Quality of Life.
    Date
    Journal International Journal of Environmental Research and Public Health
    Excerpt

    Noise is defined as an unwanted sound or a combination of sounds that has adverse effects on health. These effects can manifest in the form of physiologic damage or psychological harm through a variety of mechanisms. Chronic noise exposure can cause permanent threshold shifts and loss of hearing in specific frequency ranges. Noise induced hearing loss (NIHL) is thought to be one of the major causes of preventable hearing loss. Approximately 10 million adults and 5.2 million children in the US are already suffering from irreversible noise induced hearing impairment and thirty million more are exposed to dangerous levels of noise each day. The mechanisms of NIHL have yet to be fully identified, but many studies have enhanced our understanding of this process. The role of oxidative stress in NIHL has been extensively studied. There is compelling data to suggest that this damage may be mitigated through the implementation of several strategies including anti-oxidant, anti-ICAM 1 Ab, and anti JNK intervention. The psychological effects of noise are usually not well characterized and often ignored. However, their effect can be equally devastating and may include hypertension, tachycardia, increased cortisol release and increased physiologic stress. Collectively, these effects can have severe adverse consequences on daily living and globally on economic production. This article will review the physiologic and psychologic consequences of noise and its effect on quality of life.


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