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Biomedical subjects

D A Nelson

Publications and source records attributed to D A Nelson.

At least 91 records · Page 5Linked to original sources

Intensity discrimination in normal-hearing and hearing-impaired listeners.

Weber fractions (delta I/I) for gated 500-ms tones at 0.3, 0.5, 1, 2, and 3 kHz, and at levels of the standard ranging from absolute threshold to 97 dB SPL, were measured in quiet and in high-pass noise in five listeners with cochlear hearing loss and in three normal-hearing listeners. In regions of hearing loss, the Weber fractions at a given SPL were sometimes normal. When the Weber fractions were normal or near-normal, the addition of high-pass noise elevated the Weber fraction, strongly suggesting the use of spread of excitation to higher frequencies. Inversely, when the Weber fractions were elevated, the addition of high-pass noise produced no additional elevation, suggesting an inability to use spread of excitation. In general, the relative size of the Weber fractions, the effects of high-pass noise, and to a lesser extent, the dependence of the Weber fraction on level, were consistent with expectations based upon the audiometric configuration and the use of excitation spread. There were several notable inconsistencies, however, in which normal Weber fractions were seen at a frequency on the edge of a steep high-frequency loss, and in which elevated Weber fractions were observed in a flat audiometric configuration. Finally, when compared at the same SL, the Weber fraction was sometimes smaller in cochlear-impaired than in normal hearing listeners. This was true even in high-pass noise, where excitation spread was limited, and may reflect the unusually steep rate versus level functions seen in auditory nerve fibers that innervate regions of pathology.

Auditory Perception↗

Body composition and gonadal steroids in older white and black women.

Obesity offers protection against osteoporosis in older women. The mechanisms are not well understood, but relate in part to increased aromatization of adrenal androgens to estrone in peripheral fat and muscle tissue. Two hundred and one white and 77 black women previously reported to be free of skeletal disease and to have normal bone mass had measurements of total body bone mineral (TBBM), fat mass (TBFM), and lean mass (TBLM) performed by dual energy x-ray absorptiometry. Serum estrone, androstenedione, and dihydroepiandrostenedione sulfate were measured on the same day. Body weight, body mass index, TBFM, and TBLM were all significantly higher in the black women. However, proportionately, there were no differences in body composition between the two groups. This suggests that the black women were not more obese despite their greater body mass index, and that future studies on the health impact of obesity in older black women should take this into consideration. Despite the greater TBFM and TBLM in the black women and no difference in serum androstenedione levels, the serum estrone level was not higher in the black women, and the higher bone mass in blacks was not related to serum estrone. In both ethnic groups, TBBM was significantly related to body weight (white, r = 0.80; black, r = 0.85; P < 0.001 for both). Both TBFM and TBLM were significantly related to TBBM in both ethnic groups. Serum estrone was significantly related to all measures of body mass in the white women, but to no measures of body mass in the black women, indicating apparent differences in the metabolism of estrone between older white and black women.

Adipose Tissue↗

Sulfonylurea receptors and ATP-sensitive K+ channels in clonal pancreatic alpha cells. Evidence for two high affinity sulfonylurea receptors.

We tested for the presence of sulfonylurea receptors in pancreatic alpha cells. Two high affinity sulfonylurea receptors were identified in clonal pancreatic alpha cells (alpha TC-6): a 140-kDa species observed previously in clonal pancreatic beta cells (HIT) and a second 150-kDa protein. The dissociation constant (Kd) for both receptors is approximately 3.5 nM for an iodinated glyburide analog, 5-iodo-2-hydroxyglyburide. The estimated number of receptors (Bmax) increases approximately 2-fold, from 3.1 to 6.8 pmol/mg of membrane protein as the pH of the binding buffer is reduced from 7.5 to 6. Consistent with the notion that high affinity sulfonylurea receptors are integral components of the ATP-sensitive K+ channel, we demonstrated the presence of ATP-sensitive K+ channels in inside-out patches of alpha TC-6 cells. Whole cell K+ currents that activated with time showed inward rectification at positive potentials (above 0 mV) and were almost completely suppressed by 5 nM glyburide. Likewise, glyburide blocked 86Rb+ efflux from ATP-depleted alpha TC-6 cells, an effect that was reversed by 400 microM diazoxide. The presence of sulfonylurea receptors provides a mechanism by which sulfonylureas can directly modulate alpha cell function. The properties of the 150-kDa receptor and the role of ATP-sensitive K+ channels in alpha cells remain to be elucidated, but as in beta cells, ATP-sensitive K+ channels may be involved in metabolic regulation of alpha cells by glucose.

ATP-Binding Cassette Transporters↗

Fatal rabies associated with extensive demyelination.

OBJECTIVE: To compare the clinical course with the neuropathological findings in a patient who died of acute rabies encephalomyelitis with coexisting demyelinating lesions. DESIGN: Patient's history was extensively investigated, during her illness and after death. Details of her previous allergies, postexposure prophylaxis, early use of steroid therapy, 20-day course in an intensive care unit, and autopsy results are clinicopathologically correlated. SETTING: The intensive care unit of an 1100-bed tertiary referral center and teaching hospital. PATIENT: A 55-year-old woman, referred by her family doctor. CONCLUSIONS: Postvaccinal encephalomyelitis and rabies can run similar courses and can be misdiagnosed. On admission to the hospital, this patient was initially diagnosed as having postvaccinal disease. However, autopsy results and postmortem viral cultures disclosed a complex picture, including acute rabies and widespread perivenous demyelination. One other similar report from 1977 in the literature is reviewed. No adequate explanation of the rare coexistence of acute rabies encephalomyelitis and perivascular demyelination is available.

Demyelinating Diseases↗

Acute otitis media with transient sensorineural hearing loss. A case study.

A patient had acute otitis media with transient sensorineural hearing loss. Early symptoms included otalgia, progressive sensorineural hearing loss, and tinnitus with inflammation of the tympanic membrane. During the second week a conductive component emerged resulting in a 60-dB mixed loss in the 2- to 4-kHz region. The conductive component lasted 15 days while the sensorineural hearing loss recovered more slowly, with complete recovery at 6 months. Audiologic measures included conventional and extended high-frequency audiometry, 226-Hz and multifrequency tympanometry, binaural speech recognition, auditory brain-stem response, and psychoacoustic tuning curves.

Acoustic Impedance Tests↗

Skin color and body size as risk factors for osteoporosis.

We compared skin color, body size and bone mineral density (BMD) among three groups of postmenopausal women: 104 healthy black women, 45 healthy white women, and 52 osteoporotic white women with vertebral fractures. Skin color was measured by reflectometry, stature with a Harpenden stadiometer, weight with digital scales, and radial BMD by single photon absorptiometry. There were no significant differences in mean skin color (age-adjusted) between the healthy and osteoporotic white women, although both white groups differed from the black group. There was no significant correlation between skin color and BMD (age- and weight/height-adjusted) in any of the groups. All three groups differed significantly in age-adjusted BMD, although there was less difference between the healthy blacks and whites when covariates (body size, age) were taken into account. We further investigated body size differences by estimating stature at age 55 in all three groups based on our observations that osteoporotic women with vertebral fractures lose height at a rate that is 2.6 times faster than that of healthy aging women. Our analyses indicate that the osteoporotics were not shorter than the normals before the onset of their disease (based on estimated height), and do not have a significantly smaller body mass (weight/height and weight/height 2) than the normal white women. Additionally, the osteoporotics are above the ideal body mass index recommended by the National Institutes of Health. We conclude that fair skin is not a risk factor for osteoporosis and that large body size is not protective against the development of osteoporosis, although it may have a salutary effect on BMD in both blacks and whites.

Aged↗

Dorsal root ganglia may be reservoirs of viral infection in multiple sclerosis.

There are presently two competitive theories that attempt to explain the etiology of multiple sclerosis (MS). Briefly summarized, they are: 1. An infection, probably of viral type, may attack the oligodendroglia of the central nervous system; or, 2. An autoimmune process may begin with an infection of the peripheral lymphatic immune system, producing antibodies that cross the blood-brain barrier, leading to myelinoclasia. Since 1935, research has been directed toward myelin of the central nervous system and the myelin sheaths of peripheral nerve; however, dorsal root and cranial sensory ganglia (DRG) have apparently not been studied. The present hypothesis states that an infectious agent (probably viral) finds privileged sanctuary in the dorsal root and cranial sensory ganglia (DRG): thereafter periodically invading the spinal cord, brain, or peripheral nerve. Previously reported erratic spinal fluid viral titers and cultures can be explained by differences in the anatomy of the DRG in which there is a variable and limited contact of spinal fluid with sensory ganglia. Clues to this hypothesis were noted by the author during routine neurological examinations of patients with MS, in which sensory signs and symptoms were frequently encountered. This clinical observation has also been reported by others who found such symptoms in 75% of MS patients, ranking second only to incoordination.

Autoimmunity↗

Intraspinal therapy using methylprednisolone acetate. Twenty-three years of clinical controversy.

The intraspinal use of methylprednisolone acetate (Depo-Medrol, Upjohn Company, Kalamazoo MI) began in 1960, followed 10 years later by reports of complications. In 1960, methylprednisolone acetate was first injected by the epidural route to treat low-back syndromes. Then in 1961, the intrathecal route was more widely used to treat arachnoiditis and multiple sclerosis. Epidural therapy again came into general use in 1980 for the treatment of the failed-back syndrome because intrathecal therapy was virtually abandoned after 10 years of spirited scientific controversy. Epidural steroid therapy is now employed extensively, and there are many sanguine reports of its efficacy in treating chronic pain secondary to the failed-back syndrome, but there have also been reports of complications. This review was prompted by recent manufacturer warnings, as well as by an ongoing heated controversy in Australia regarding its use epidurally. During the last 30 years, one can define 5 instructive historical parallels between intrathecal and epidural steroid therapy, and this historicity points up several principles that should govern any further epidural therapy with methylprednisolone acetate. This critical chronologic review surveys neurosurgical use from 1960 to 1970, neurologic use from 1970 to 1980, and anesthesiology use from 1980 to present.

Anesthesiology↗

Development and current use of ASTM/HL7 messages for health care communications in the USA.

Two influential organizations in the development of medical data exchange standards in the United States of America are ASTM and HL7. A shared message structure has been adapted to diverse applications including hospital information systems and clinical laboratories. The basic approach is the exchange of ASCII messages. Messages segments relate to clinical entities and support a hierarchy of entities. Individual data fields are of variable length and bounded by delimiter characters. The feasibility of this approach has been confirmed by its adoption by a number of medical institutions and information system vendors.

Clinical Laboratory Information Systems↗

Specificity of photolabeling of beta-cell membrane proteins with an 125I-labeled glyburide analog.

The interaction between sulfonylureas and membrane proteins from a hamster insulin-secreting tumor (HIT) cell line has been examined. Four HIT cell membrane proteins were covalently linked to an 125I-labeled glyburide analog by photolabeling. Three photolabeled polypeptides of M(r) 65,000, 55,000, and 30,000 were identified as low affinity "glyburide receptors." These proteins appear to be of similar abundance, when quantitated by photolabeling, with half-maximal displacements (Ki values) by glyburide, glipizide, and tolbutamide in the low micromolar range. The glyburide analog is more tightly bound to a M(r) 140,000 protein with dissociation constants, determined by filtration binding assays and by photolabeling, of 7 and 9.0 nM, respectively. The labeled analog was displaced from the M(r) 140,000 protein by glyburide, glipizide and tolbutamide with Ki values of 3.3 nM, 103 nM, and 25 microM, respectively, as estimated by photolabeling. Optimal conditions established for visualizing the M(r) 140,000 band on autoradiograms prepared after UV cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis include irradiating the radioligand-receptor complex at 1.5 J/cm2 at 312 nm, followed by heating samples in pH 9.0 sodium dodecyl sulfate-gel sample buffer. With receptor sites partially occupied (5 nM radioligand), approximately 0.75% of the protein is photocoupled to the radioligand and visualized by autoradiography. Our results confirm that the M(r) 140,000 polypeptide contains the beta-cell high affinity glyburide binding site and show that the second generation sulfonylurea antidiabetic drugs have a selective increase in affinity for this receptor.

Animals↗

Composite index of skeletal mass: principal components analysis of regional bone mineral densities.

Principal components analysis is a statistical method that is used to reduce and explore data to facilitate further analyses. This method was applied to bone mineral densities measured at seven sites in 109 black and 44 white women, ages 22-80, at an internal medicine clinic in urban Detroit. We excluded subjects with a history of diseases or drugs known to affect bone metabolism. Principal components analysis was used to summarize the interrelationship of the densities and yielded two major results. First, the seven site measurements were reduced to a single, composite index (PC1) of skeletal mass that accounted for 73% of the variation in density among subjects. PC1 had roughly equal weights among the sites. A second combination of the seven sites indicated that the contrast between axial and appendicular regional densities accounted for another 10% of the variation among subjects. In investigating the relationship of density to age, body mass index, and ethnic group, we found that the principal components composite index had a stronger correlation with age (r = -0.58) and with body mass index (r = 0.34) than almost all of the regional densities. Black-white differences were larger for the composite index than for any single site density. A multiple regression of the composite index on ethnicity, body mass index, and age yielded a larger R2 (0.46) than any of the individual site densities. The second principal component, although of theoretical interest, showed a minimal ability to discriminate among subjects using the three independent variables of this study.

Absorptiometry, Photon↗

Outcome variables in osteoporosis trials.

The conduct of controlled clinical trials examining the anti-fracture efficacy of potential therapies for osteoporosis is a relatively new and developing science. We have reviewed several aspects of data acquisition, emphasizing that bone mass measurement and, similarly, back pain can only be regarded as ancillary outcome variables. Serial measurement of stature when performed in a precise manner may be an inexpensive, quick, and convenient surrogate outcome variable, most applicable to large multi-center studies. The only true end-point of such trials is the radiographic documentation of new vertebral fracture occurrence. Techniques for obtaining serial radiographs and assessing vertebral morphometry with good quality control have been described. Important questions still need to be resolved concerning the most appropriate criteria for defining incident fractures and for calculating fracture frequency. Implications regarding trial sample size requirements are discussed.

Body Height↗

Distortion-product emissions and auditory sensitivity in human ears with normal hearing and cochlear hearing loss.

Distortion product emissions (DPEs) at 2f1-f2 frequencies were measured in 53 human ears; 21 of them exhibited cochlear hearing loss. DPEs were obtained as a function of stimulus level (DPE growth curves) at seven frequency regions between 707 Hz and 5656 Hz. Several distinctly different shapes or patterns of DPE growth curves were observed. These included single-segment monotonic growth curves with and without saturation at moderate and high stimulus levels, diphasic growth curves with nulls at moderate stimulus levels, and non-monotonic growth curves with negative slopes at high stimulus levels. Low-level, irregularly shaped segments were more frequent in normal-hearing ears, suggestive of normal low-level active nonlinearities from the outer-hair-cell subsystem. High-level, steeply sloped segments were frequent in hearing-impaired ears, suggestive of residual nonlinearities from a cochlear partition without functional outer hair cells. The stimulus level at which the DPE could just be distinguished from the noise floor, the DPE detection threshold, demonstrated moderate positive correlations (r's from 0.50 to 0.81) with auditory thresholds when all ears, both normal and impaired, were considered together. Those correlations were not strong enough to quantitatively predict auditory thresholds with any great accuracy. However, DPE thresholds were able to predict abnormal auditory sensitivity with some precision. DPE thresholds correctly predicted abnormal auditory sensitivity 79% of the time in the present study, and up to 96% of the time in previous studies. These results suggest that DPE thresholds may prove useful for hearing screening in cases where cooperation from the subject is limited or where corroboration of cochlear hearing loss is required. Different patterns of DPE growth curves suggest underlying micro-mechanical differences between ears, but the differential diagnostic value of those patterns remains to be determined.

Acoustic Stimulation↗

Temporal cues for consonant recognition: training, talker generalization, and use in evaluation of cochlear implants.

Limited consonant phonemic information can be conveyed by the temporal characteristics of speech. In the two experiments reported here, the effects of practice and of multiple talkers on identification of temporal consonant information were evaluated. Naturally produced /aCa/disyllables were used to create "temporal-only" stimuli having instantaneous amplitudes identical to the natural speech stimuli, but flat spectra. Practice improved normal-hearing subjects' identification of temporal-only stimuli from a single talker over that reported earlier for a different group of unpracticed subjects [J. Acoust. Soc. Am. 82, 1152-1161 (1987)]. When the number of talkers was increased to six, however, performance was poorer than that observed for one talker, demonstrating that subjects had been able to learn the individual stimulus items derived from the speech of the single talker. Even after practice, subjects varied greatly in their abilities to extract temporal information related to consonant voicing and manner. Identification of consonant place was uniformly poor in the multiple-talker situation, indicating that for these stimuli consonant place is cued via spectral information. Comparison of consonant identification by users of multi-channel cochlear implants showed that the implant users' identification of temporal consonant information was largely within the range predicted from the normal data. In the instances where the implant users were performing especially well, they were identifying consonant place information at levels well beyond those predicted by the normal-subject data. Comparison of implant-user performance with the temporal-only data reported here can help determine whether the speech information available to the implant user consists of entirely temporal cues, or is augmented by spectral cues.

Adult↗

Sensory symptoms of multiple sclerosis may be clues to causation: review and a hypothesis.

Sensory signs and symptoms occur in 75 percent of patients with multiple sclerosis (MS), ranking second to coordination defects. After intensive research into MS began in the 1930s, most attention was devoted to central nervous system demyelination. Some studies were done on peripheral nerve, but none on the sensory ganglia of the cord or brain. An original and thus far uninvestigated hypothesis is presented here that an unidentified organism might reside and multiply in various dorsal root and cranial sensory ganglia (DRG). This review summarizes the sensory signs and symptoms of multiple sclerosis, traces the embryology and physiology of DRG, and describes the present day research status of human demyelination produced by a number of viral infections. If the infectious agent for MS exists in a latent state in the DRG, low spinal fluid viral titers and sporadic cultures of certain viruses might be explained by the occasional contact of spinal and cranial sensory ganglia with spinal fluid flow. Research techniques available to test the hypothesis are as follows: various heating reactions and evoked potential testing of patients, and viral hybridization-transcription techniques applied to DRG obtained at autopsy. The "Decade of the Brain" became law on July 25, 1989, when President Bush signed Joint House Resolution 174. The forward looking declaration calls upon citizens and scientists alike to dedicate themselves for the next ten years to the task of eliminating various neuropsychiatric diseases that decimate many populations. High on the list is multiple sclerosis (MS), the subject of a new hypothesis presented here.(ABSTRACT TRUNCATED AT 250 WORDS)

Ganglia, Spinal↗