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Biomedical subjects

J M Miller

Publications and source records attributed to J M Miller.

At least 271 records · Page 15Linked to original sources

Effect of endolymphatic hydrops on capsaicin-evoked increase in cochlear blood flow.

Capsaicin, which causes release of neuropeptides including substance P, has been shown to cause dose-related increases in cochlear blood flow (CBF). Since CBF regulation is altered in animal models with endolymphatic hydrops, this study was designed to examine the effect of hydrops on capsaicin-induced CBF changes. CBF responses to 0.01 and 0.001% capsaicin applied to the round window membrane were measured in normal and 12-week hydropic guinea pigs using laser Doppler flowmetry. With 0.01% capsaicin, CBF increased by only 13 +/- 7.8% in the hydropic ear, compared with 34% +/- 13% in the normal animal (p = 0.027). With 0.001% capsaicin, CBF increased by only 7.5 +/- 4.2% in the hydropic ear, compared with 28 +/- 16% in the normal ear (p < 0.001). These findings demonstrate a reduced responsiveness to capsaicin with endolymphatic hydrops and suggest that hydrops causes an alteration in the peptidergic sensory fibers of the inner ear or in the vascular smooth muscle or both. The results are consistent with previous reports of reduced vascular responsiveness in hydropic guinea pigs and provide further evidence for abnormal CBF regulation in hydrops.

Alkaloids↗

Abortion in heifers inoculated with a thymidine kinase-negative recombinant of bovine herpesvirus 1.

The Copper isolate of bovine herpesvirus 1 (BHV-1) was used to produce a thymidine kinase-negative (TK-) recombinant by insertion of a beta-galactosidase (bgal) expression cassette into the TK coding region. The recombinant virus (TK- bgal+) was tested for abortifacient activity in cattle by inoculation of 5 pregnant heifers at 25 to 29 weeks gestation. Five additional heifers were inoculated with the Cooper TK-positive (TK+) virus to serve as controls. After inoculation, both groups of heifers developed similar febrile responses and neutralizing antibody titers. Virus was isolated from blood of all heifers during the first postinoculation (PI) week, and isolation frequencies were similar for both groups. In contrast, whereas virus was isolated from many of the nasal and vaginal swab specimens of heifers inoculated with TK+ virus, only rare virus isolations were made from the heifers given TK- bgal+ virus. All heifers inoculated with TK+ virus aborted between PI days 19 and 35. The finding of characteristic microscopic lesions and viral antigen in fetal tissues indicated that the abortions were caused by BHV-1 infection. Virus was isolated from 3 fetuses, and all isolates were TK+ virus. Two heifers inoculated with TK- bgal+ virus aborted at PI days 25 and 39. Fetal tissues had typical BHV-1 microscopic lesions and viral antigen. Virus was isolated from blood of both fetuses, and the isolates were TK- bgal+. Results of this study indicate that inactivation of the TK gene reduces, but does not eliminate, the abortifacient activity of BHV-1.

Abortifacient Agents↗

Quantification of the Brückner test for strabismus.

PURPOSE: To measure quantitatively the change in the coaxial fundus reflex with varying degrees of ocular misalignment. METHODS: The coaxial fundus reflex was imaged with a charge coupled device camera under conditions of simulated ocular misalignment ranging from 0 degrees to 7 degrees of fixation eccentricity. The effects of refractive error and pupil size were controlled. Average gray scale brightness values were calculated for each bright pupil image after some image processing was performed on the raw images. RESULTS: A reliable, sharply delineated, minimum brightness at foveal fixation was observed. CONCLUSIONS: It is estimated that this technique can be automated to detect the presence of 2 degrees to 3 degrees of ocular misalignment based on the difference in brightness of the bright pupil images between the two eyes.

Adult↗

Magnetic resonance imaging of the functional anatomy of the superior oblique muscle.

PURPOSE: To study the size and contractile changes of the normal superior oblique (SO) muscle using high-resolution magnetic resonance imaging (MRI), and to evaluate the abnormalities in these characteristics produced by SO palsy. METHODS: Multiple coronal MRI image planes were obtained using a surface coil to span the antero-posterior extent of each orbit and were repeated in multiple directions of gaze. Digital image analysis was used to measure muscle cross-sectional area for evaluation of size and contractility. RESULTS: Data for 16 orbits of 11 subjects without SO palsies established norms for morphology and contractility. On SO contraction in down gaze, maximum cross sectional area was significantly (P < 0.001) greater than on relaxation in up gaze, and the point of maximum cross-section shifted posteriorly with contraction. In seven subjects with clinically unilateral chronic SO palsies, the affected muscle was significantly smaller than normal (P < 0.001) and lacked contractile changes; clinically normal fellow SO muscles exhibited normal cross-sections and contractile changes. CONCLUSION: High-resolution MRI, coupled with quantitative morphometric analysis, can demonstrate the size and contractility of the normal SO muscle. The technique, which can be employed using widely available clinical equipment, is also sensitive enough to detect anatomic and functional changes expected in chronic SO palsies.

Adolescent↗

Evidence for fibromuscular pulleys of the recti extraocular muscles.

PURPOSE: Magnetic resonance imaging (MRI) shows that the paths of recti extraocular muscle (EOM) bellies remain fixed in the orbit during large ocular rotations and across large surgical transpositions of their insertions. These findings imply that recti EOMs pass through pulleys coupled to the orbit and anterior to the muscle bellies, because the insertions must move with the globe. The present study was conducted to locate anatomically and to characterize histologically the pulley tissues. METHODS: High-resolution MRI images were collected from volunteers, using multiple gaze directions to infer the locations of, and occasionally to visualize, recti EOM pulleys. Fresh cadaver orbits were exenterated and dissected to evaluate mechanical and structural properties of the orbital connective tissues. Lipid was cleared from whole specimens to reveal tissue relationships. Other specimens were selectively step- and serial-sectioned for histochemical and immunohistochemical staining. RESULTS: Magnetic resonance imaging demonstrated dense connective tissue structures within posterior Tenon's fascia near the equator of the globe adjacent to the recti EOMs. Histochemistry showed these structures to be pulleys--fibroelastic EOM sleeves consisting of dense bands of collagen and elastin, suspended from the orbit and adjacent EOM sleeves by bands of similar composition. A monoclonal antibody to human smooth muscle alpha-actin demonstrated substantial smooth muscle in the pulley suspensions and in posterior Tenon's fascia. Tenon's fascia itself was seen to be suspended at its periphery from the orbital walls like a drumhead. CONCLUSIONS: The human orbit contains specialized musculofibroelastic tissues in and just posterior to Tenon's fascia that serve as compliant pulleys and determine the pulling directions of recti EOMs. In this sense, the pulleys are the functional origins of the recti EOMs and are determinants of ocular motility.

Actins↗

On Okinawa.

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History, 20th Century↗

In Korea, then home.

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History, 20th Century↗

Neuronal regulation of cochlear blood flow in the guinea-pig.

1. Previous studies have shown that electrical stimulation (ES) of the guinea-pig cochlea causes a neurally mediated increase in cochlear blood flow (CBF). It is known that the centrifugal neuronal input to the cochlea comes through the perivascular sympathetic plexus from the cervical sympathetic chain and along the vestibular nerve (VN) from the periolivary area of the brainstem. Both of these neuronal systems are distributed topographically in the cochlea. 2. In order to study the neural origins of ES-evoked CBF increase, laser Doppler flowmetry was used to test the following hypotheses. (a) The response is regional, that is, limited to the area of the cochlea stimulated. To test this we performed differential ES of the cochlear turns. CBF was measured from either the third or the first turn. (b) The response is mediated via autonomic receptors within the cochlea. To study this, we applied atropine, succinylcholine and idazoxan locally to the cochlea. (c) The response is influenced by neuronal input via the sympathetic cervical chain (SC) and components of the VN. We stimulated and sectioned the SC, and sectioned the VN, to test this hypothesis. 3. We observed that the CBF response was topographically restricted to the stimulated region. Locally applied muscarinic or nicotinic antagonists (atropine and succinylcholine respectively) did not affect the response. However, local idazoxan (an alpha 2-blocker) eliminated the response. Locally applied adrenaline and SC stimulation modified the dynamic range of the response. SC sectioning enhanced the responsiveness of the cochlear vasculature to ES. The VN section caused a temporary decrease in CBF and elimination of the ES-evoked CBF response. 4. We conclude that the release of dilating agents is topographical with respect to ES current flow, the ES-evoked CBF increase is peripherally mediated via alpha 2-receptors, and the response is influenced by input via the SC. The elimination of the response by VN sectioning proximal to the brainstem indicated that fibres of the VN mediate the CBF increase during direct cochlear ES. The data suggest that these fibres may be the efferent limb of a neural loop involved with the regulation of CBF. Such a system could provide a mechanism for the rapid increase in CBF with organ stress.

Adrenergic alpha-Antagonists↗

Basal nitric oxide production in regulation of cochlear blood flow.

Nitric oxide (NO), recently identified as endothelium-derived relaxing factor, has been shown to influence both vascular and neural function. In blood vessels, NO is produced by endothelial and smooth muscle cells and may play a role in regulation of cochlear blood flow. In the central nervous system, NO functions as a neurotransmitter involved in long term potentiation. The principle hypothesis tested in this study was that basal NO production in the cochlear blood vessels contributes to regulation of CBF. Since NO is a vasodilator, diminished NO synthesis may decrease the level of CBF. Application of a competitive inhibitor of NO synthase either intravenously or to the round window membrane caused a reduction in CBF. The application to the round window membrane did not affect compound action potential thresholds. With intravenous administration, the effect on CBF was dose-related and could be reversed with the physiologic substrate, L-arginine. These data indicate that NO is produced in the cochlear blood vessels and contributes to the regulation of CBF.

Action Potentials↗

Cochlear blood flow measured by averaged laser Doppler flowmetry (ALDF).

This report describes a new approach to estimate the hydromechanical properties of a vascular system. Averaged laser Doppler flowmetry (ALDF) was developed by averaging the flux signal of a laser Doppler flowmeter (LDF) synchronized to the heart cycle. The usefulness of this method was verified by manipulation of the cochlear microvasculature. Twelve pigmented guinea pigs under pentobarbital/fentanyl anesthesia were used. The cochlea was surgically exposed and the LDF probe placed on the bony surface of the first turn to monitor cochlear blood flow (CBF). The LDF flux signal (0.2 s time constant) was sampled by an A/D board at 2 kHz for 255 ms and averaged with synchronization to the heart beat. The mean blood flow, peak to peak amplitude, and time (phase) delay of pulsatile flow were measured from the averaged signal. According to a transmission line model of the vascular system, under a given perfusion pressure, mean flow reflects resistance while amplitude and time delay of the pulsatile flow are related to the reactance component of the impedance of the vascular system. During the formation of photochemically-induced thrombosis in the cochlear microvasculature, there was a dramatic mean flux decrease (90.1 +/- 3.4% from baseline (BL), N = 6). Additionally, a time-dependent decrease in amplitude and time delay of pulsatile flow were indicated by ALDF. These results suggest a large increase in vascular resistance and significant decrease in compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗