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Biomedical subjects

J M Miller

Publications and source records attributed to J M Miller.

At least 343 records · Page 19Linked to original sources

Videographic Hirschberg measurement of simulated strabismic deviations.

PURPOSE: To demonstrate the potential use of subpixel image processing methods to perform automated Hirschberg measurements of strabismic deviations using relatively inexpensive personal computer hardware; to determine if the method might allow screening for strabismus using full-face video images obtained from a distance of 1 meter. METHODS: Strabismic deviations (< 25 prism diopters) were simulated by means of induced asymmetric fixation. A ring of coaxial infrared light-emitting diodes (LED) were used to generate first Purkinje reflexes. Computerized image analysis with subpixel processing was used to measure the locations of the first Purkinje reflexes and pupil centers of video images of 10 normal subjects, following the technique of the clinical Hirschberg test. The apparent strabismic deviation was calculated from the relative asymmetry of the center of the corneal reflex ring to the pupil center in each eye. RESULTS: In 10 normal subjects, there was a statistically significant linear correlation of Hirschberg horizontal reflex deviation with asymmetric fixation pseudo-esotropia (0.85 > or = r2 > or = 0.99, P < 0.05). CONCLUSIONS: The Hirschberg test is used manually to detect strabismus in infants and children but requires a highly skilled examiner. The image processing method described here requires no operator interpretation and may make the test more applicable. The results suggest that this technology may be appropriate for a screening instrument.

Adult↗

Betahistine-induced vascular effects in the rat cochlea.

Betahistine (BH) has been used widely to treat cochlear disorders, such as tinnitus and Meniere's disease. The mechanism of action of BH in the cochlea is assumed to be based on its histamine-like effect on H1 receptors in the cochlear vasculature, leading to an increased cochlear blood flow (CBF). Recently it has been shown that BH can strongly affect H3 heteroreceptors (a novel histamine receptor subclass) in the periphery, via an autonomic ligand. This mechanism may also contribute to the BH effects on CBF. This study was to validate BH effects in the cochlear vasculature and to investigate the possible mechanisms of action of this drug in the inner ear vasculature. We assessed the effects of BH on CBF with the laser Doppler flowmeter in 23 rats and concluded that BH affects vascular conductivity in the cochlea in a dose-dependent fashion; betahistine diffuses through the round window, but does not have access to vascular receptors or ligands once in the labyrinthine fluids; and the H1 receptors mediate the systemic and peripheral vascular effects of BH, whereas the cochlear effect involves cholinergic receptors.

Animals↗

A handheld calculator program for determination of gene transfer between races.

Methods of statistical analysis have permeated all biomedical fields, but the advent of inexpensive handheld calculators has enabled those individuals unskilled in advanced mathematics to make competent analyses. Statistics cannot be avoided in genetics and their evaluations, really estimated, are essential to further knowledge and understanding. Older scientists had to rely on the use of paper and pencil to derive formulas and then apply them. The experience gained in this one small area of investigation has been presented in detail to help other investigators who do not possess a broad mathematical background.

Black People↗

The first American medical school.

John Archer, a physician from Harford County, was one of the graduates of the first medical school on American soil-Philadelphia College-in 1768. The names of the initial instructors, including John Morgan, William Shippen, and Thomas Bond, and of the first graduates, including John Archer and Jonathon Potts, are well known to most medical historians. Many of these early American physicians had a deep sense of political commitment, and placed conscience and love of country above their medical practices.

History, 18th Century↗

The effect of peripheral loading with kynurenine and probenecid on extracellular striatal kynurenic acid concentrations.

Kynurenic acid (KYA) is the only known endogenous excitatory amino acid antagonist in mammalian brain. In the present study we examined the effects of precursor loading with kynurenine (KYN) and blockade of organic acid transport with probenecid, either alone or in combination, on extracellular striatal KYA concentrations in unanesthetized rats. Baseline KYA concentrations were 1.61 +/- 0.29 pmol/ml. Following administration of KYN 150 mg/kg with increasing doses of probenecid a maximal increase in KYA to 946 +/- 210 pmol/ml was seen with probenecid 200 mg/kg. Probenecid 200 mg/kg alone increased KYA levels to 16.0 +/- 5.2 pmol/ml. The combination of probenecid 200 mg/kg with KYN 450 mg/kg produced a maximal increase of KYA to 2085 +/- 391 pmol/ml, a 1300-fold increase indicating marked potentiation. These results show that pharmacologic manipulation can markedly increase extracellular fluid concentrations of KYA into a range which may be useful in attempts to block NMDA receptor-mediated neurotoxicity.

Animals↗

An optimal reference plane to detect glaucomatous nerve fiber layer abnormalities with computerized image analysis.

Nerve fiber layer height measured with respect to a standardized retinal reference plane is diminished by glaucoma. The definition of the reference plane influences the nerve fiber layer measurements. We empirically determined the best reference plane for measurement of nerve fiber layer height. Optimal parameters for measurement reproducibility were determined for a group of 6 normal and 6 glaucomatous eyes each imaged nine times. Optimal ability to distinguish normal from glaucomatous eyes was determined for a group of 33 normal eyes and 36 glaucomatous eyes each imaged once. Measurements with the smallest variability (root mean square error = 32 microns) and the highest sensitivity (83%) and specificity (88%) were achieved when the reference plane is defined by portions of the image from a peripheral temporal area 32 degrees wide, and for two peripheral nasal areas of 55 degrees width centered 30 degrees above and below horizontal. These parameters for the definition of the reference plane should provide measurements of nerve fiber layer height with the least variability and the greatest ability to discriminate between eyes with early glaucomatous damage and normal eyes.

Glaucoma↗

Latency and reactivation of a thymidine kinase-negative bovine herpesvirus 1 deletion mutant.

A bovine herpesvirus 1 (BHV 1) mutant variant with a deletion in the thymidine kinase (TK) gene was assessed for its ability to establish latency and be reactivated in cattle. After treatment with dexamethasone, reactivated TK- BHV 1 was isolated from one of four cattle that received virus by intravenous inoculation only, and from four of four cattle that received virus by intranasal, intravaginal, and intravenous inoculation. Results prove that TK- BHV 1 will establish latency and can be reactivated in the natural host.

Animals↗

Comparison of dynamic image and pulsed Doppler ultrasonography for the diagnosis of the small-for-gestational-age fetus.

OBJECTIVE: Because poor fetal growth is a significant cause of perinatal morbidity and mortality, a prospective study was undertaken to evaluate the ability of real-time ultrasonography and Doppler velocimetry to detect the small-for-gestational-age fetus. STUDY DESIGN: A prospective study of 136 women at risk for fetal growth abnormalities was conducted. Patients were delivered within 3 weeks and had live-born, nonanomalous, singleton infants. The relative estimated fetal weight (estimated fetal weight divided by the median birth weight for gestational age) and the systolic/diastolic ratio were measured and compared with receiver-operator characteristic curves. In this method the area under the curve is the index of performance. RESULTS: Forty-six infants were small for gestational age. Although both relative estimated fetal weight (area under the curve = 0.923) and systolic/diastolic ratio (area under the curve = 0.837) were significantly associated with the small for gestational age fetus, the former was more strongly correlated, p = 0.021. CONCLUSION: Relative estimated weight is more sensitive and specific and should be the preferred parameter when gestational age is known.

Blood Flow Velocity↗

Extraocular muscle forces in alert monkey.

We describe an extraocular muscle (EOM) force transducer that provides low-noise signals from an alert animal for several months, is implanted without disinserting the muscle, and is well-tolerated by the body, and present results obtained with the device. The transducer can be used to study orbital statics and dynamics, and oculomotor control signals undiminished by orbital low-pass filtering and antagonistic pairing of muscles. It may provide an index of effective EOM innervation, useful in studies of orbital tissue healing and plasticity, and oculomotor (OM) signal adaptation. During horizontal saccades transducers implanted in the lateral rectus (LR) and medial rectus (MR) of a monkey trained to fixate revealed an agonist muscle tension waveform corresponding to the "pulse-slide-step" pattern of saccadic innervation, and an antagonist waveform that was similar within a scale factor. We never observed transient increases in antagonist force at the ends of saccades (active braking) or at the beginnings. Onset of saccadic force in LR preceded that in MR by 1.6 msec for abducting saccades, and lagged that in MR by 1.1 msec for adducting saccades. During vertical saccades, transient force changes were found in LR and MR, which were likely due, at least in part, to globe translation. LR and MR forces during fixation tended to be largest with the eye about 10 degrees in elevation, and smallest in depression, indicating that effective total innervation was a function of vertical gaze, or that there was variation in the elastic component of muscle force related to orbital geometry, with LR and MR innervation independent of vertical gaze. An exponential decrease in fixation force, having a time constant of about 10 days, was observed after implantation. This may have reflected adaptive muscle lengthening or post-surgical healing.

Animals↗

Percutaneous absorption of benzyl acetate through rat skin in vitro. 2. Effect of vehicle and occlusion.

The effect of vehicle and occlusion on the in vitro percutaneous absorption of [methylene-14C]-benzyl acetate (1.7-16.6 mg/cm2) has been studied in diffusion cells using full thickness skin from male Fischer 344 rats. Absorption of neat benzyl acetate through rat skin occluded with parafilm was 49.3 +/- 2.0% (mean +/- SD, n = 4) after 48 hr. When benzyl acetate in ethanol was applied to the skin and the skin was occluded with parafilm, the extent of absorption at 48 hr was not significantly different from that after neat application. However at 6 hr, as the ethanol content of the application mixture was increased, the absorption of benzyl acetate through occluded skin was enhanced proportionally (r = 0.999). When phenylethanol was used as a vehicle, the extent of the benzyl acetate absorption through occluded skin at 48 hr was enhanced (P less than 0.05) compared with that after application neat; with 50% (v/v) phenyl-ethanol, absorption at 48 hr was 56.3 +/- 4.9%. However, this enhanced absorption did not correlate with the proportion of phenylethanol in the application mixture. When dimethylsulphoxide was used as a vehicle, the extent of absorption of benzyl acetate through occluded skin at 48 hr was enhanced (P less than 0.05) compared with that after application neat (absorption was 59.3 +/- 3.7% of the applied dose when 50% (v/v) dimethylsulphoxide was used). As the dimethylsulphoxide content of the application mixture was increased, the absorption of benzyl acetate was enhanced proportionally. Occlusion of the skin surface with parafilm often significantly enhanced absorption (P less than 0.05), although the effect varied with time and vehicle. In general, the degree of any enhanced absorption caused by the use of a vehicle or occlusion of the skin was small, and, in most cases, would be unlikely to be toxicologically significant.

Animals↗

Cochlear blood flow in response to dilating agents.

Reduced cochlear blood flow (CBF) has been implicated in various pathologies of the inner ear, including sudden deafness, noise-induced hearing loss and Meniere's disease. Thus the aim of some current therapeutic regimens to treat these conditions is to increase CBF and thereby improve oxygenation of the inner ear tissues. Most of the vasodilating agents in clinical use, however, do not have specific experimental evidence to support their effects on CBF. The hypotension which can follow systemic administration may limit their local effectiveness and general utility, just as it complicates the interpretation of the data in animal experiments. In the current study we investigated the effect of six agents, known for their systemic cardiovascular actions, on CBF: hydralazine, sodium nitroprusside, papaverine, nicotinic acid, verapamil and histamine. The effect of these drugs was studied after topical applications on the round window membrane (RWM) and systemic intravenous administrations. CBF was monitored with a laser Doppler flowmeter (LDF). Topical administration of sodium nitroprusside was the most effective in increasing CBF, followed, in order, by hydralazine and histamine. No change in CBF was observed for papaverine, verapamil or nicotinic acid. Systemic administrations of all the agents caused a marked decrease in blood pressure and variable effects on CBF. We discuss the CBF changes in relation to the different pharmacological mechanisms of action of each drug. The study demonstrates the effectiveness of topical application of vasodilating agents in increasing CBF.

Administration, Topical↗

Cochlear electrode reimplantation in the guinea pig.

Cochlear implants are being applied to an ever widening patient population, including children in whom lifetime use of these devices is anticipated. Replacement of implants can be expected for reasons of device failure as well as future upgrading. This investigation was undertaken to examine the effect of cochlear electrode explanation and reimplantation on spiral ganglion cell survival. Guinea pigs with normal ears were initially implanted and either explanted or explanted and reimplanted (at 2 months) with a single wire ball-tip intracochlear electrode or a silastic carrier (each remaining for an additional 2 months). Little loss of hair cells or auditory nerve was observed across experimental groups and normal controls. Restricted basal turn cochlear and spiral ganglion cell loss was observed in a few animals in each group and was likely associated with mechanical damage from initial implantation. Likewise the scattered organ of Corti damage and hair cell loss observed was noted in only a few cochleae in each experimental group. Therefore, no significant differences in the average pathology across experimental groups and controls were observed. Thus, explantation or explantation with subsequent reimplantation does not appear to constitute an additional significant pathological risk compared to implantation alone.

Animals↗

The influence of loud sound on red blood cell velocity and blood vessel diameter in the cochlea.

Using intravital microscopy, we observed both decreases in red blood cell velocity and possible vasoconstriction in stria vascularis capillaries of the rat cochlea in response to loud sound (Quirk et al., 1991). However, our observation of vasoconstriction was subject to error in measurements from the two dimensional images obtained with our silicon intensified (SIT) camera due to the influence of focus causing image blur. The purpose of the current study was to apply an extended focus microscopy technique to obtain quantitative assessment of vessel diameter changes (Avinash et al., 1992), as well as to extend these studies to the guinea pig model. Broad-band sound stimulation at intensities of 84 dB SPL and 110 dB SPL were used. The results show that loud sound induces a sequence of changes in cochlear blood flow. Stimulation with 110 dB SPL resulted in a mean increase (maximum = 27%) in red blood cell velocity for the first 20 min of exposure followed by a gradual decrease below baseline (minimum = -12%) prior to termination of the signal. This velocity decrease and subsequent recovery were associated with significant changes in vessel diameters of selected and measured capillaries. In contrast, the 84 dB SPL stimulus caused an increase in red blood cell velocity (maximum = 20%) and vessel diameter (mean = 7.5) during the stimulation period. No recovery was observed during the 10 min observation period following sound. Several possible mechanisms responsible for these changes are discussed.

Acoustic Stimulation↗