Abraham Shulman

Leupeptin protects sensory hair cells from acoustic trauma

Calpains, a family of calcium activated proteases, promote the breakdown of cellular proteins, kinases, phosphatases and transcription factors. Calpain inhibitors attenuate some neurodegenerative processes in certain cell types. Here we show that leupeptin, a potent calpain inhibitor, protects the sensory hair cells in the inner ear from acoustic overstimulation (48 h, 100 or 105 dB SPL, octave band noise at 4 kHz). Acoustic overstimulation caused a significant increase in calpain immunolabeling in the sensory epithelium suggesting a possible role in noise-induced cochlear degeneration. Infusion of leupeptin into the inner ear significantly reduced the amount of sensory cell loss from acoustic overstimulation. However, leupeptin did not protect against hair cell loss from the ototoxic drug, carboplatin.

Antral fibromyxoma presenting as a giant nasal polyp

Abstract A case of fibromyxoma, apparently antral in origin, presenting as a giant nasal polyp and associated with malar swelling and mild unilateral exophthalmos has been reported. Similar clinical findings in association with this uncommon tumor have not, to our knowledge, been published previously.

Leupeptin reduces impulse noise induced hearing loss

BackgroundExposure to continuous and impulse noise can induce a hearing loss. Leupeptin is an inhibitor of the calpains, a family of calcium-activated proteases which promote cell death. The objective of this study is to assess whether Leupeptin could reduce the hearing loss resulting from rifle impulse noise.MethodsA polyethelene tube was implanted into middle ear cavities of eight fat sand rats (16 ears). Following determination of auditory nerve brainstem evoked response (ABR) threshold in each ear, the animals were exposed to the noise of 10 M16 rifle shots. Immediately after the exposure, saline was then applied to one (control) ear and non-toxic concentrations of leupeptin determined in the first phase of the study were applied to the other ear, for four consecutive days.ResultsEight days after the exposure, the threshold shift (ABR) in the control ears was significantly greater (44 dB) than in the leupeptin ears (27 dB).ConclusionLeupeptin applied to the middle ear cavity can reduce the hearing loss resulting from exposure to impulse noise.

Electrophysiology quantitative electroencephalography/low resolution brain electromagnetic tomography functional brain imaging (QEEG LORETA): Case report: Subjective idiopathic tinnitus - predominantly central type severe disabling tinnitus.

The clinical significance of QEEG LORETA data analysis performed sequentially within 6 months is presented in a case report of a predominantly central type severe disabling subjective idiopathic tinnitus (SIT) before and following treatment. The QEEG LORETA data is reported as Z-scores of z = ± 2.54, p < 0.013. The focus is on demonstration of patterns of brain wave oscillations reflecting multiple brain functions in multiple ROIs in the presence of the tinnitus signal (SIT). The patterns of brain activity both high, middle and low frequencies are hypothesized to reflect connectivities within and between multiple neuronal networks in brain. The Loreta source localization non auditory ROI Images at the maximal abnormality in the very narrow band frequency spectra (24.21 Hz), showed the mathematically most probable underlying sources of the scalp recorded data to be greatest in the mid-cingulate, bilateral precuneus, cingulate and the bilateral caudate nucleus. Clinical correlation of the data with the history and course of the SIT is considered an objective demonstration of the affect, behavioral, and emotional component of the SIT. The correlation of the caudate activity, SIT as the traumatic event with the clinical course of PTSD, and the clinical diagnosis of PTSD is discussed. The clinical translation for patient care is highlighted in a SIT patient with multiple comorbidities by translation of QEEG/LORETA electrophysiologic data, as an adjunct to: provide an objectivity of patterns of brain wave activity in multiple regions of interest (ROIs) reflecting multiple brain functions, in response to and in the presence of the tinnitus signal, recorded from the scalp and analyzed with the metrics of absolute power, relative power, asymmetry, and coherence, for the subjective tinnitus complaint (SIT); 2) provide an increase in the accuracy of the tinnitus diagnosis; 3) assess/monitor treatment efficacy; 4) provide a rationale for selection of a combined tinnitus targeted therapy of behavioral, pharmacologic, sound therapy modalities of treatment attempting tinnitus relief; 5) provide insight into the medical significance of the SIT; 6) attempt discriminant function analysis for identification of a particular diagnostic clinical category of CNS neuropsychiatric disease; and 7) attempt to translate what is known of the neuroscience of sensation, brain function, QEEG/LORETA source localization, for the etiology and prognosis of the individual SIT patient.

Brain Imaging and tinnitus

The theme of the AAO HNS Martha Entenmann, Abraham Shulman, M.D., Barbara Goldstein, PhD, International Tinnitus Miniseminar 2012 was “Brain Imaging and Tinnitus. The meeting, well attended , provided to the attendees a take home message that clinical application of the brain imaging technologies of nuclear medicine, single photon emission tomography, (SPECT), photon emission tomography(PET), functional MRI brain imaging ,fMRI, magnetoencephalography, (MEG), can provide an objectivity for tinnitus, a subjective sensory aberrant auditory complaint.

Controlled Cortical Impact-induced Neurodegeneration Decreases after Administration of the Novel Calpain-inhibitor Gabadur

One aspect of secondary injury in traumatic brain injury is the marked increase in intracellular calcium and resultant over-activation of the calcium-dependent neutral cysteine protease calpain. Gabadur is a novel protease inhibitor with calpain-inhibition properties formulated from the classic protease inhibitor leupeptin linked to a pregabalin carrier. This construction allows the entire compound to cross the blood-brain barrier after peripheral administration to better target the site of injury. In this study, a single intraperitoneal dose of Gabadur was administered immediately following controlled cortical impact injury in rats. Neocortical slices were examined at 48 h post-injury via Fluoro-Jade B staining, revealing an improvement in cortical neurodegeneration in Gabadur treated rats. Levels of detrimental active calpain-2 measured via western blot were also decreased in rats receiving Gabadur. This data supports the benefit of targeted protease inhibition in the treatment of traumatic brain injury.

A Tribute to Robert W. Entenmann (Bob)-12/10/16

Robert W. Entenmann, age 88, passed on 9/15/16. His beloved daughter Jacquelyn reported that he had returned home from a fishing trip to the Bahamas. He suffered a fall at home in Lauderdale by the Sea in Florida from which he did not recover. His passion was boating and fishing. He was part of the Entenmann family who came from Germany to the USA, whose grandfather started a baked goods company in Brooklyn, and which as a family, father, mother, and he together with his brother, achieved the American Dream. The baked goods were well appreciated locally for their excellence of quality and taste. Over the years the family prospered, but never forgot its start, and always gave back to family, friends and community. Mr. Entenmann demonstrated to all the moral example of dedication to family, and charitable contributions to science and community. He retired from the family business after it was sold in 1978. He purchased a Sound Avenue potato farm soon after and turned it into a farm to raise thoroughbred race horses, known as “Big E Farm.” In 1995, he planted 18 acres of vitisvinifera, the first steps in creating Martha Clara Vineyards, which he named for his mother. In all his ventures his successes reflected what coworkers and managers said: “He was always about sharing something, “a real pleasure to work for”. The establishment of the Long Island First Investors, by Mr. Entenmann, together with Robert Rosenthal and his team reflects the vison of a leader and team builder interested not only in oneself but community.

AAO HNS Tinnitus Miniseminar "Tinnitus Lessons Learned from Combat and Service". Summary 2015.

The theme of the AAO-HNS Tinnitus Miniseminar, 09/23/2014, was “Tinnitus Lessons Learned from Combat and Service.” The speakers discussed their clinical experiences as well as lessons learned from combat and service for translation to tinnitus theory, basic science and clinical research, and tinnitus patient diagnosis and treatment. The program chairman and moderator was: - Michael E. Hoffer, M.D., F.A.C.S., Professor of Otolaryngology, Department Otolaryngology HNS, University of Miami

The Use of Implants in the Management of Tinnitus

Program Description: Tinnitus is one of the most common health problems in the United States and recent figures show that tinnitus is increasing in frequency. As otolaryngologists we are the primary specialty responsible for the diagnosis and management of tinnitus. Despite a great deal of work in this area definitive treatment options for tinnitus are lacking in many cases. Recognizing the importance of this issue the AAO-HNSF and the Martha Entenmann Tinnitus Foundation have endowed a series of miniseminars to address tinnitus. This year’s panel will once again be comprised of national and international experts who will discuss advances in tinnitus treatment using implantable devices. The panel will discuss the use of cochlear implants, implantable hearing aids, and other, more novel, implantable devices. In particular the presenters will focus on the physiologic basis for tinnitus response to electrical or mechanical stimulation, cases series and outcomes, and patient selection for various treatments. The panel will finish by discussing several cases and will provide time for audience questions. Educational Objectives: 1) Better understand treatment options for tinnitus. 2) Better understand the principals that support the use of electrical stimulation in tinnitus. 3) Provide a more clear understanding of the impact of cochlear implants on tinnitus.

Tinnitus neural map; A positron emission tomography study

The neural map of tinnitus involves more than the classical auditory pathways and the limbic system. PET findings in six patients, with severe problem tinnitus, revealed the involvement of the cerebellum, insula and frontal cortices when these patients were imaged before and after high frequency bone conduction therapy. The frontal cortex and cerebellum demonstrated the highest ratios of metabolic change but changes were also noted in the thalamus and the medial temporal lobe system. The PET data supports the view that the frequency specific map of auditory cortex is dynamic and can change with high frequency therapy, presumably due to neural reorganization. The PET data further reflect alterations in multiple areas of brain in all patients to tinnitus and/or high frequency therapy. Encouraging was the observation that patients with the most dramatic change in their global pre/post PETs were also the ones who exhibited the greatest behavioral improvement in regards to tinnitus relief measured by informal ...