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Biomedical subjects

M S Marion

Publications and source records attributed to M S Marion.

At least 19 recordsLinked to original sources

Sensorineural hearing loss caused by NSAID-induced aseptic meningitis.

Aseptic meningitis is a rare complication of nonsteroidal anti-inflammatory drug (NSAID) use. Otologic symptoms may include sensorineural hearing loss and tinnitus. A 66-year-old woman sought the care of an otologist for sudden bilateral sensorineural hearing loss and a substantial increase in baseline tinnitus. The patient had previously undergone a left tympanoplasty secondary to cholesteatoma and had been treated for atypical face pain with ibuprofen taken every six hours for three months. Magnetic resonance imaging (MRI) with gadolinium demonstrated abnormal enhancement of the dura mater and the surrounding basal cisterns, with extension of enhancing dura mater into the internal auditory canals. Cerebrospinal fluid examination revealed evidence of aseptic meningitis. An audiogram confirmed new bilateral sensorineural hearing loss. Hearing loss and tinnitus resolved and no abnormalities were observed with MRI when nonsteroidal anti-inflammatory medication was discontinued. Otolaryngologists are well aware of the otologic sequelae in patients with meningitis. However, NSAIDs need to be considered as possible causal agents in the evaluation of meningitis with otologic symptoms.

Aged

Conservative management of acoustic neuroma: an outcome study.

OBJECTIVE: This study analyzed selection criteria, clinical outcome, and tumor growth rates in patients with acoustic neuromas in whom the initial management strategy was observation. METHODS: A retrospective review of patients with conservatively managed unilateral acoustic neuromas was conducted. Minimum follow-up was 6 months. Patients with neurofibromatosis Type II were excluded. Differences in tumor growth rates were analyzed by use of the Wilcoxon rank sum test. RESULTS: Sixty-eight patients (31 men and 37 women) with a mean age of 67.1 years were followed for an average of 3.4 years after diagnosis. The reasons for a trial of observation included advanced age (55%), patient preference (21%), minimal symptoms (9%), poor general medical condition (7%), asymptomatic tumor (4%), and tumor in the only hearing ear (4%). Fifty-eight patients (85%) were successfully managed with observation alone. Ten patients (15%) ultimately required treatment (nine received microsurgical treatment and one patient underwent radiosurgical intervention) at a mean time interval of 4.0 years after diagnosis. Forty-eight tumors (71%) showed no growth and 20 (29%) enlarged during the study period. The mean tumor growth rate at the 1-year follow-up was significantly higher in the group requiring treatment (3.0 mm) than in the group not requiring treatment (0.36 mm) (P < 0.0001). Thus, the tumor growth rate at the 1-year follow-up was a strong predictor of the eventual need for treatment. CONCLUSION: Observation is a reasonable management strategy in carefully selected patients with acoustic neuromas. Diligent follow-up with serial magnetic resonance imaging is recommended, because some tumors will enlarge to the point at which active treatment is required.

Aged

Novel degradation pathway of glycated amino acids into free fructosamine by a Pseudomonas sp. soil strain extract.

A Pseudomonas sp. soil strain, selected for its ability to grow on epsilon-(1-deoxyfructosyl) aminocaproic acid, was induced to express a membrane-bound enzymatic activity which oxidatively degrades Amadori products into free fructosamine. Apparent Km values for fructosyl aminocaproate, epsilon-fructosyl lysine, fructosyl glycine, and ribated lysine were 0.21 mM, 2.73 mM, 3.52 mM, and 1.57 mM, respectively. The enzyme was also active against alpha-fructosyl lysine and borohydride-reduced Amadori product, weakly active with ribated and glycated polylysine, and inactive with reducing sugars, amino acids, and glycated proteins. The enzymatic activity was highest at pH 6.5 and 25 degrees C in 0.1 M sodium phosphate, while over 80% of the activity was lost above 65 degrees C. Complete inhibition was observed by HgCl2, NaN3, and NaCN suggesting a role for SH groups and copper in the enzymatic activity. The reaction products were characterized by 1H NMR, 13C NMR, and GC/MS and found to correspond to 1-deoxy-1-aminofructose, i.e. free "fructosamine," and adipic acid. Confirmation of the free fructosamine structure was based on the complete spectroscopic identity of the borohydride reduction product with commercially available glucamine (1-amino-1-deoxyglucitol). The new enzyme is provisorily classified as fructosyl N-alkyl amino acid oxidase (EC 1.5.3) (fructosyl-amino acid:oxygen oxidoreductase) and may thus belong to a novel class of "Amadoriases" which deglycate Amadori products oxidatively. In contrast, however, the new enzyme acts on the alkylamine bond rather than the ketoamine bond of the Amadori product.

Amino Acids

Aphysiologic performance on dynamic posturography.

The remarkable ability of the body to maintain balance is the result of central nervous system integration of sophisticated inputs from the vestibular, visual, and somatosensory systems. Strategies by patients with balance dysfunction are aphysiologic when their performance is relatively better on more difficult conditions of sensory conflict than on easier ones. Twenty-two aphysiologic patterns on computerized dynamic posturography were compared with age-matched normal and vestibular patterns. The aphysiologic group performed significantly better than the patients in the vestibular dysfunction group on the most difficult subtests of computerized dynamic posturography, conditions 5 and 6, yet significantly poorer on the easier subtests, conditions 1 through 4. In addition, patients in the aphysiologic group tended to show greater intertrial variability compared with patients in both normal and vestibular system dysfunction groups. A stepwise linear discriminant analysis was used to determine a set of conditions that had significant value in discriminating between the three patient groups. Case studies are presented to further illustrate the clinical usefulness of computerized dynamic posturography testing in the evaluation of patients suspected of having a functional component to their on-feet balance problems.

Adult

Isolation, purification, and characterization of an Amadori product binding protein from a Pseudomonas sp. soil strain.

Sugars react nonenzymatically with protein amino groups to form a ketoamine adduct (Amadori product), which leads to the formation of advanced glycation end-products. These compounds are involved in the development of tissue modifications such as cross-linking and fluorescence in diabetes and aging. Searching for an enzyme to reverse protein glycation, we isolated a Pseudomonas sp. soil strain growing selectively on the Amadori product epsilon-fructosyl-aminocaproate. An Amadori product binding protein (ABP) was purified from the bacterial extract by single-step affinity chromatography on glycated lysine-Sepharose. The protein, a monomer of 45 kDa, did not bind to unglycated or NaBH4-reduced glycated lysine-Sepharose suggesting specificity for the Amadori compound. The concentration-dependent binding of glycated aminocaproate showed saturation with Kd = 1.49 microM and Bmax = 17.63 nmol/mg of protein corresponding to 0.8 mol/mol of protein. The binding of epsilon-1-[14C]fructosyl-aminocaproate to the protein was inhibited by other glucose-derived Amadori products, but not by free sugars, unglycated amines, or ribated lysine. The sequence of the first 16 NH2-terminal amino acids and a GenBank search revealed that ABP is a novel protein. Its synthesis was inducible by growth of the organism in Amadori product. Immunoblotting studies showed that ABP is not found in cell extracts from other prokaryotes, yeast, or liver homogenate and does not bind Amadori products in glycated proteins. ABP has no enzymatic activity toward glycated substrates and may thus have transport or permease function for glycated amino acids.

Amino Acid Sequence

Immunoelectron microscopic analyses of Maillard reaction products in bovine anterior lens capsule and Descemet's membrane.

It has been hypothesized that Maillard reaction products form in basement membranes during aging and may affect protein turnover. The purpose of this study was to localize Maillard reaction products in intact lens capsules and Descemet's membranes by immunoelectron microscopy to determine whether Maillard products accumulated with age and whether basement membrane thickness increased to a similar degree. The monoclonal antibodies antiglucitollysine and antipyrraline were employed to detect the products in native and glucose-treated bovine basement membranes. The content of basic amino acids, furosine, and fluorophores (370/440), as well as resistance to trypsin digestion showed that the basement membranes formed significant quantities of Maillard products when incubated with 200 mM glucose in vitro (P < 0.05). Likewise, incubation in 200 mM glucose resulted in at least a 4-fold increase in immunoreactivity (P < 0.001). Native basement membranes increased in thickness more than 2-fold with age (P < 0.001). Immunoreactivity varied similarly in that bound antiglucitollysine increased approx. 2-fold and antipyrraline approx. 3-fold in old vs. young basement membranes, but these differences were significant only in pyrraline immunoreactivity in the lens capsule (P < 0.01). Advanced products other than pyrraline may accumulate in Descemet's membrane since significant increases in fluorescence and resistance to trypsin were noted. These data suggest that the Maillard reaction may, to a small degree, contribute to basement membrane thickening.

Aging

Familial paragangliomas of the head and neck.

OBJECTIVE: It has been known for some time that paragangliomas of the head and neck may be familial. Recent evidence suggests genomic imprinting is an important factor in the clinical development of these tumors. In genomic imprinting the imprintable gene is transmitted in a mendelian manner, but expression of the gene is determined by the sex of the transmitting parent. In the case of paragangliomas, the gene does not result in the development of tumors when maternally inherited. The purpose of this study was to determine if this hypothesis correctly predicted the inheritance pattern of familial paraganglioma in a large series of patients. SETTING: A retrospective review of case records of the Mayo Clinic, Rochester, Minn, a tertiary referral center, was performed for the years 1950 to 1992 to identify patients with familial paragangliomas of the head and neck. PATIENTS: A total of 38 patients with familial paragangliomas of the head and neck were identified in nine kindreds. RESULTS: Carotid body tumors were the most common paragangliomas of the head and neck (34 cases). Glomus jugulare or glomus vagale occurred in eight cases. In 16 (42%) of the patients there were multiple tumors. Surgical complications, primarily cranial nerve palsies, were more frequent for tumors larger than 5 cm in diameter. CONCLUSIONS: An autosomal dominant inheritance pattern could be shown for paragangliomas of the head and neck that was consistent with genomic imprinting. It is recommended that all individuals in kindreds with paragangliomas be screened after the age of 16 years to detect early asymptomatic tumors.

Adolescent

Tinnitus.

Tinnitus, a common complaint, reportedly affects more than 37 million Americans. Most often, it is associated with a sensorineural hearing loss in the high-frequency range. Tinnitus, however, is a symptom and not a disease. Complacency about this symptom complex may cause physicians to overlook a severe underlying pathologic process. Patients with unilateral tinnitus, pulsatile tinnitus, fluctuating tinnitus, or tinnitus associated with vertigo should undergo thorough assessment, including elicitation of a complete history, physical examination, and audiologic analysis. In many instances, treatment is effective. Masking of tinnitus, medical therapy, and biofeedback and counseling are some measures that have been used in the management of tinnitus.

Biofeedback, Psychology

Labyrinthitis ossificans: histopathologic consideration for cochlear implantation.

Labyrinthitis ossificans may be a hindrance to cochlear implantation by making electrode insertion difficult. We performed a histopathologic study of 24 temporal bones with labyrinthitis ossificans from multiple causes. The organ of Corti was graphically reconstructed and the degree of obstruction was estimated for each millimeter of the cochlea. Correlations were calculated between the degree of new bone formation and the cause, patient's age and sex, and time from the original temporal bone insult. Our results demonstrate that complete cochlear ossification is rare. The scala tympani in the basal turn of the cochlea is the most frequent area of ossification, regardless of the cause of the labyrinthitis ossificans. Meningogenic labyrinthitis, usually a childhood disease, was associated with the greatest amount of ossification. When ossification resulted from tympanogenic labyrinthitis, the scala tympani was completely ossified near the round window niche in all temporal bones. Neo-ossification of the basal turn associated with otosclerosis was limited to the proximal 6 mm of the scala tympani in all cases. Three temporal bones had a patent round window niche and basal turn, but significant apical and middle-turn ossification. Peripheral sensorineural elements were severely degenerated in the region of the ossification in all specimens, and spiral ganglion cell counts were decreased.

Adolescent

Ganglion cell populations in labyrinthitis ossificans.

Ossification of the perilymphatic spaces of the inner ear is frequently found in patients with profound deafness who may be candidates for cochlear implantation. The ossification may be a hindrance in electrode insertion and has previously been considered a relative contraindication to implantation. The quantity of peripheral auditory elements remaining in a series of patients with labyrinthitis ossificans has not been reviewed. We performed a histopathologic study of 16 temporal bones with partial cochlear ossification of multiple etiologies. The organ of Corti and spiral ganglion were graphically reconstructed. The degree of obstruction was estimated for each millimeter of the scala tympani and scala vestibuli. A quantitative evaluation of the sensorineural elements of the inner ear (spiral ganglion cells, inner and outer hair cells, and peripheral auditory axons) was performed. The results were compared with 16 control patients with normal hearing and no evidence of cochlear ossification. Our results show that the greatest amount of damage is found in the organ of Corti with preservation of a significant number of spiral ganglion cells in most cases. A wide range of ganglion cells (6,310 to 28,196) was found in patients with labyrinthitis ossificans with the mean number of ganglion cells being 17,152. A profound sensorineural hearing loss was noted in all patients except one. Meningogenic labyrinthitis and otosclerosis were associated with the greatest loss of ganglion cells. The location of ossification could be correlated with the region showing loss of the organ of Corti. In the majority of patients, the location of ossification and fibrosis could not be correlated with the region of the spiral ganglion showing loss of ganglion cells. The implications of these findings for cochlear implantation is discussed.

Adolescent

Histopathologic evaluation of adipose autografts in a rabbit ear model.

Injection of autologous adipose tissue removed via liposuction has been used clinically for facial contouring, the aging face, furrows, facial atrophy, acne scars, nasolabial folds, chin, and various other surgical defects. Survival rates for autografts of fat have been quoted anywhere from 30% to 80%. Our study uses a reproducible rabbit animal model for autotransplantation of adipose tissue and examines the histopathologic changes that occur to the graft over time. Autogenous subcutaneous fat was removed from a dorsal scapular donor site, treated to stimulate cannula damage as in liposuction, then reinjected at the base of the ear. Histologic examination of the grafts were made at 5, 10, 15, 20, 40, and 100 days after transplantation. Hematoxylin-eosin sections were graded on degree of fibrosis present (0 to 4+), viable fat (1 to 10), degree of inflammation (0 to 4+), and neovascularization (+ or -). Viability of fat decreased from 8.5 to 10 at 5 days to 2 viability at 40 days. Acute inflammation peaked at 10 days, followed by the chronic inflammatory response with macrophages and multinucleated giant cells scavenging the dying fat graft. Neovascularization began at 5 days, peaked at 10 days, and remained constant thereafter only at the edge of the graft. Microcysts appeared at 15 days and increased in number in proportion to the decrease in viable fat. In summary, the temporal histologic events are progressive fibrosis; decreased amount of viable fat; inflammation beginning with a neutrophilic response, later a macrophage and giant cell response; and neovascularization at the periphery of the graft insufficient to maintain graft viability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue

Three-dimensional reconstruction of the temporal bone.

Study of the complex anatomy and pathology of the temporal bone has traditionally used microscopy which permits analysis in only two dimensions. Recent advances in bioimaging technology have permitted visualization and reconstruction of computed tomography images in three dimensions. We have developed a technique that applies this technology in the imaging and reconstruction of human temporal bones. Data taken from serial histologic sections of the temporal bone are entered into a computer. The sections are edited and, through the use of specially developed software, a realistic three-dimensional reconstruction is produced. The reconstructed image can be rotated along any of three axes, and structures within the temporal bone can be isolated for more detailed analysis. Applications for the study of pathologic conditions of the temporal bone will be discussed.

Adult

Ultrastructural analyses of acellular glomerular basement membranes and mesangial matrix in a spontaneously diabetic rhesus monkey.

Renal changes similar to those considered diagnostic for diabetes in humans are infrequently observed in spontaneous noninsulin-dependent (NID) diabetic monkeys. In the current study, renal cortical tissue blocks are rendered acellular to demonstrate glomerular basement membrane (GBM) and mesangial matrix (MM) changes in a naturally occurring NID diabetic rhesus monkey (Macaca mulatta). Transmission electron micrographs of these specimens show axial MM accumulations with numerous striated collagen fibrils that frequently extend onto internal (endothelial) surfaces of peripheral GBM. The outer (epithelial) component, although compact, appears bilaminar due to folded external surfaces not coinciding with similar irregularities on internal surfaces. By scanning electron microscopy, external surfaces of sclerotic GBMs are extensively wrinkled and, following cryofracture, show congestion and expanded MM. A fenestrated meshwork of MM, which appears less dense and compact than epithelial BM, extends from axial regions onto GBM internal surfaces. The true thickness of randomly sampled peripheral GBM thickness (approximately 400 nm) is approximately double that of normal rhesus GBM. Diabetic GBMs exhibit ruthenium red positivity for surface polyanions with linear site densities not significantly different from normal. These observations indicate that sclerotic GBMs in diabetic rhesus monkeys closely resemble those seen in human end-stage diabetic glomerulopathy and suggest that this nonhuman primate may offer an excellent model for studies of chronic diabetic BM disease.

Animals