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Biomedical subjects

W L Meyerhoff

Publications and source records attributed to W L Meyerhoff.

At least 37 records · Page 2Linked to original sources

The effect of cyclophosphamide on development of experimental cholesteatoma.

BACKGROUND: Recent work has shown that middle ear application of propylene glycol in chinchillas produces an inflammatory reaction resulting in cholesteatoma formation in 50% to 70% of animals. This study was done to determine if cyclophosphamide, an immune suppressor and anti-inflammatory agent, is capable of inhibiting cholesteatoma development in the animal model. METHODS: Ten adult chinchillas received systemic cyclophosphamide (20 mg/kg per day) for 14 days. On days 5, 8, and 11 of that period, the animals also received bilateral middle ear applications of 60% propylene glycol (0.2 mL per ear). Four weeks after the first propylene glycol application, the animals were killed for histologic evaluation. RESULTS: Eight of the 10 animals survived the full 4-week study period, providing 16 temporal bones for evaluation. It was found that cyclophosphamide reduced the leukocyte counts; however, middle ear inflammation appeared unaffected. Cholesteatoma occurred in eight (50%) of the 16 ears studied, and histologic findings were essentially identical to those previously seen in animals given propylene glycol alone. CONCLUSION: Under the conditions of this study, cyclophosphamide had no effect on cholesteatoma development in the animal model.

Administration, Topical↗

Pathology of otitis media.

Otitis media is characterized by inflammation of the middle ear. The pathologic changes seen in this condition tend to occur on a continuum, progressing from acute and subacute stages to the chronic phase, in which irreversible tissue damage is observed. The earliest morphological changes involve the lamina propria of the middle ear mucosa and include increased capillary permeability, edema, and leukocytic infiltration. During the late acute to subacute stages, the mucosa also tends to show a marked increase in numbers of ciliated and secretory epithelial cells. As the inflammatory process enters the chronic phase, there is a continuing shift in the population of infiltrating leukocytes toward increasing numbers of mononuclear cells that secrete substances that facilitate tissue destruction and fibrosis. There is also development and proliferation of granulation tissue, which is intimately involved in the process of bone erosion. As granulation tissue matures, it becomes denser and less vascular--a process that leads to permanent fibrosis and formation of adhesions that may significantly compromise middle ear function. Other pathologic entities occasionally associated with chronic otitis media include cholesteatoma, cholesterol cysts and granuloma, and tympanosclerosis, all of which may contribute to irreversible alterations of middle ear structure.

Bone Resorption↗

Perilymphatic fistula.

Perilymph fistula is recognized as a clinically significant problem in certain patients. Owing to its lack of specific symptoms, diagnosis is difficult and depends upon a combination of historical data, physical findings, and test results. Early treatment is initiated in patients with overwhelming evidence of perilymph fistula, in order to ameliorate vestibular symptoms and preserve auditory function. Patients with subtle symptoms, however, should not be overlooked, because they will also benefit from the treatment of this disease.

Fistula↗

Loss of perilymph affects electrocochleographic potentials in the guinea pig.

Alterations of electrocochleographic (ECoG) potentials recorded from guinea pig cochleae have been reported to occur following round window (RW) membrane perforation (perilymphatic fistula). To further evaluate the pathophysiology of perilymphatic fistula, a study was conducted of the short-term effects of acute RW membrane perforation on the amplitude of the summating potential (SP) and the action potential (AP), and the SP:AP ratio. Acute RW membrane perforation was produced in 15 Hartley guinea pigs. The animals were placed in a head dependent position, so that some perilymph would drain from the inner ear following RW perforation. For both click and low frequency tone burst stimuli (2 kHz), the mean AP amplitudes showed variable but progressive deterioration with time following RW membrane perforation. Action potential latencies showed a significant increase with time for both click and tone burst stimuli. Summating potential amplitudes for click and tone burst were typically stable or slightly decreased. Interanimal variability of all measures was typically high. However, AP and SP amplitudes in the same animal were consistently and differentially affected by perforation of the RW membrane. There also were differential effects on the positive and the negative components of the SP, suggesting the interplay of several generator mechanisms. The authors conclude that AP amplitude and, consequently, the SP:AP ratio are sensitive to the creation of a perilymphatic fistula. These results provide support for the use of ECoG tests in the diagnosis of perilymphatic fistula.

Animals↗

Spontaneous perilymphatic fistula: myth or fact.

Controversy exists surrounding the diagnosis of spontaneous perilymphatic fistula. In an effort to help resolve this controversy the author conducted a review of the literature as well as a review of 212 of his patients who underwent surgical exploration for suspected perilymphatic fistula. Interpretation of the literature reviewed was hampered by the lack of a uniformly accepted definition for the word spontaneous. Dorland's Medical Dictionary defines spontaneous as that which occurs without external influence. Webster's Dictionary, on the other hand, provides a much more confining definition of the word by stating that a spontaneous event is one that occurs or is produced by its own energy. Only 58 percent of the author's 212 patients had an antecedent history of an external event that may have precipitated the suspected perilymphatic fistula (trauma, flying, diving) while almost 41 percent recalled an antecedent event of internal origin (lifting, straining, sneezing, nose blowing). If one were to support the definition of spontaneous provided by Dorland's Medical Dictionary, then the 41 percent of patients who had no antecedent history of external event would have to be considered as having spontaneous perilymphatic fistula. If, on the other hand, one were to endorse the definition of spontaneous provided by Webster's then less than 2 percent of the author's patients would have to be considered as having spontaneous perilymphatic fistula.

Adolescent↗

Intrasubject test-retest variability in clinical electrocochleography.

Seventeen healthy volunteers without a history of auditory or vestibular difficulty and with normal screening audiometry had bilateral (34 ears) electrocochleography performed repeatedly at 1-week intervals. Each subject had from four to seven electrocochleograms performed on each ear. Measurements were made in the external auditory canal using a gold-foil "TIPtrode." Amplitude and latency for the summating potential (SP) and action potential (AP) were measured and SP/AP ratios were calculated. Averages and standard deviations for amplitude, latency, and SP/AP ratios were computed. The average SP/AP ratio was 0.22 with a standard deviation of 0.06. The range was 0.04 to 0.50. The average difference between the highest and lowest SP/AP ratio for a given individual was 0.155 (i.e., the range 0.03 to 0.31) with a standard deviation of 0.07. These normative data are useful in assessing the results of dehydration electrocochleography and in establishing how much test-retest variation is required to suggest pathology.

Action Potentials↗

Ototoxicity of topical agents.

Topical otic preparations are commonly prescribed by otolaryngologists--head and neck surgeons. It is well documented in the literature that some agents in these preparations are ototoxic when applied to the middle ear in experimental animals, although the occurrence of ototoxicity in the clinical setting is controversial. This article discusses topical otic preparations currently available as well as various other agents. The clinician should prescribe these preparations with close surveillance for potential ototoxicity.

Administration, Topical↗

Modified occipital approach to the endolymphatic sac and cochlear aqueduct of the guinea pig.

Obliteration of the endolymphatic sac reliably results in endolymphatic hydrops in some animal species. While this procedure is frequently utilized in the study of experimental Meniere's disease, additional information regarding inner ear fluid hydrodynamics can be obtained by obstructing the cochlear aqueduct to eliminate the influence of the cerebrospinal fluid on the perilymphatic compartment of the inner ear. This report describes a modified extradural occipital approach for surgical obliteration of the endolymphatic sac and obstruction of the cochlear aqueduct in the guinea pig. The extradural approach allows direct visualization of the cochlear aqueduct without manipulation or retraction of the dura, sigmoid sinus, or cerebellum. For experimental studies, which require obliteration of both the endolymphatic sac and cochlear aqueduct, this approach provides improved reliability with reduced morbidity and mortality.

Animals↗

Complications of lumbar spinal fluid drainage.

Cerebrospinal fluid fistula is an unfortunate, yet well-recognized, complication of basilar skull fracture, skull base surgery, and neurotologic procedures. Treatment commonly involves the use of continuous lumbar drainage. A retrospective chart review of 32 consecutive patients who required placement of lumbar drain by the otorhinolaryngology and neurosurgical services from March 1988 through July 1991 was undertaken to assess possible complications. The complications found were readily separated into minor and major categories on the basis of the possibility of permanent morbidity or mortality. Minor complications, including subjective complaints of headache, nausea, vomiting, etc., were noted in 59% of patients. Major complications were observed in four of 32 patients (12.5%), including unilateral occlusion of the posterior cerebral artery and unilateral true vocal cord paralysis. Alleviation of all complications was achieved by cessation of lumbar drainage. These cases are presented with discussion of pathogenesis. These findings demonstrate the possibility of potentially serious complications that mandate close monitoring of patients who require continuous lumbar drainage.

Adult↗

Modified Rambo meatoplasty in translabyrinthine tumor removal.

Spinal fluid otorrhea and otorhinorrhea are morbid complications that occur in up to 18% of patients after removal of translabyrinthine tumor. Both of these problems can be significantly reduced if, during the initial surgery, the posterior canal wall is taken down and the tympanic membrane and external auditory canal skin are removed for better exposure of the eustachian tube orifice. The external auditory meatus can then be sealed by a previously described modification of the Rambo procedure. This additional procedure adds about 20 minutes to the surgery and presents a small risk of retained squamous epithelium. Fifty consecutive patients were divided into two equal groups and studied retrospectively. In group I, the patients underwent a modified Rambo meatoplasty at the time of the removal of their translabyrinthine tumor, whereas patients in group II had the tympanic orifice of their eustachian tube obstructed through the facial recess. Review of the postoperative course of these fifty patients indicated that the addition of the modified Rambo meatoplasty was justified by the overall reduction in morbidity and expense it provided.

Adult↗

Catastrophic otologic injury from oral jet irrigation of the external auditory canal.

Jet irrigation is an accepted method for removal of cerumen from the external auditory canal. Even at a submaximal power setting, oral jet irrigators can generate enough force to rupture the tympanic membrane. Parameters for safe use of these irrigators have never been established. Three cases are reported in which, in addition to tympanic membrane rupture, oral jet irrigators caused ossicular disruption, round and oval window fistulae, and subluxation of the stapedial footplate. A prospective study performed on 25 fresh cadavers demonstrated a 6% incidence of tympanic membrane perforation when the power setting was one-third full power or greater. Recommendations are made for safe use of oral jet irrigators for removal of external auditory canal cerumen.

Aged↗

Tympanic membrane microstructure in experimental cholesteatoma.

This study assessed changes in tympanic membrane microstructure associated with cholesteatoma development following middle ear application of 50% propylene glycol in chinchillas. Although the epidermal layer of the tympanic membrane (TM) was destroyed immediately after propylene glycol application, the epidermal basal lamina remained intact and appeared to serve as a substrate for regrowth of epidermis over the TM. During the initial phase of epidermal repair (4 to 7 days after propylene glycol administration), pseudopodial processes from the epidermal cells occasionally penetrated the basal lamina; however, no migration of epidermis into the lamina propria occurred at that time. The basal lamina remained largely intact until about 2 weeks, when it became fragmented in some areas, so that sizable gaps appeared. Hyperplastic epidermal cells then migrated through the gaps into the rapidly proliferating connective tissue of the lamina propria. At 2 to 4 weeks, degenerative changes were observed in portions of the fibrous layer, which underwent phagocytosis by foreign body giant cells. This process created defects in the fibrous layer which permitted invasion of epidermis to the medial portion of the lamina propria. The epidermis subsequently reached the medial side of the TM in areas where there was incomplete repair of the mucosal layer.

Animals↗

Ototoxicity of an ototopic preparation--experimental results and clinical facts.

The ototoxicity of "Cortisporin Otic Suspension" containing 3.5 ml neomycin base, 10,000 units/ml polymyxin B was studied using the baboon (papio ursinus) as an experimental animal. Inner and outer hair cell loss occurred in all cochleas of the ears which received cortisporin. Most lesions were confined to the basal turn of the organ of Corti. Separate evaluation of polymyxin B and neomycin at the same concentration as in cortisporin showed that polymyxin B produced greater cochlear damage. The results of this study and clinical reports of sensorineural hearing loss due to commercially available ear drops indicate that ototopical preparations must be used with caution in clinical situations in which they may reach the middle ear.

Animals↗

Effect of topical fosfomycin on polymyxin B ototoxicity.

Fosfomycin is an antibiotic that has been found to reduce the ototoxicity of aminoglycoside antibiotics and cisplatin when systemically coadministered. Polymyxin B, an antibiotic frequently used in ototopical preparations, has been shown to be ototoxic in experimental studies. To investigate the effect of fosfomycin on polymyxin B ototoxicity, topical administration of the two agents into the middle ear cavity was performed. Two groups of chinchillas were used. One group received applications of polymyxin B alone, and the second group received polymyxin B combined with fosfomycin. It was found that application of polymyxin B produces severe damage to the cochlea. However, when polymyxin B was given in combination with fosfomycin, cochlear damage was dramatically reduced. It is likely that in clinical use, a combination of polymyxin B and fosfomycin would demonstrate reduced risk of ototoxicity.

Administration, Topical↗

A patient-oriented approach to perilymph fistula.

The subject of perilymph fistula is controversial in part because the preoperative diagnosis of perilymph fistula is difficult. Patients suffering auditory and vestibular symptoms secondary to perilymph fistula, therefore, present a dilemma to the practicing physician. In some instances, patients with auditory and vestibular symptoms in the absence of perilymph fistula will be subjected to middle ear exploration without benefit, while in other instances patients with auditory and vestibular symptoms secondary to perilymph fistula will be denied surgical treatment. Auditory and vestibular symptoms are a quality of life issue. Therefore, in an effort to provide care of the highest quality the patient must be actively involved in the decision process. Such involvement can be meaningful only after the patient is carefully counseled as to the pros and cons of surgery, as well as the alternatives. A prognostic paradigm based on the personal experience of one of us (W.L.M.) with perilymph fistula patients is described and is used in patient consultation in an effort to facilitate decision making.

Fistula↗

Summating potential/action potential ratio in perilymph fistula.

A prospective study of electrocochleography in patients with clinically suspected perilymph fistula was undertaken to determine its predictive value in that disorder. One hundred forty-four patients suspected of having perilymph fistula had electrocochleography performed--34 of these (39 ears) had exploratory tympanotomy. Of the 19 ears with normal preoperative summating potential/action potential (SP/AP) ratio, ten had perilymph fistula identified at the time of surgery. Of the 20 ears with abnormal SP/AP ratio, 16 had perilymph fistula confirmed at exploration, 18 had resolution of symptoms after oval window and round membrane grafting, and only one ear had postoperative persistence of the abnormal SP/AP ratio. This study suggests that an abnormal SP/AP ratio is not only predictive of endolymphatic hydrops, but also of perilymph fistula (both problems of inner ear fluid imbalance). This study also suggests that, while abnormal SP/AP ratio is fairly specific for inner ear fluid imbalance, it is not sensitive.

Adolescent↗