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Biomedical subjects

R S Baker

Publications and source records attributed to R S Baker.

At least 55 records · Page 3Linked to original sources

Kinematic analysis of eyelid movements in patients recovering from unilateral facial nerve palsy.

We assessed eyelid function by subjective clinical examination and quantitative means in patients recovering from facial nerve palsy. Electromagnetic search coil techniques were used to record the concurrent movements of the two eyelids to study alterations in blink main sequence (peak velocity versus amplitude) relationships and interocular differences in eyelid kinematics. After onset of unilateral palsy, the paresis of eyelid closure showed varying degrees of recovery. Adaptive increases in blink main sequence slope contributed to maximizing closure of the paretic eyelid. However, blink adaptation mechanisms must operate bilaterally, as there also was evidence of altered main sequence slope in the nonparetic eyelid. In general, main sequence slope was inversely related to the level of eyelid paresis. The highest indices of blink adaptation were in those patients with moderate paresis, and main sequence slope was decreased in those patients with increasing degrees of recovery. The assessment of eyelid function with search coil techniques provides a sensitive means of monitoring disease and treatment course. Data also aid understanding of adaptive gain control in the neural control of blink in health and disease.

Adaptation, Physiological↗

Structure-function correlations in the human medial rectus extraocular muscle pulleys.

PURPOSE: Fibroelastic pulleys function like the trochlea to fix the position and pulling direction of the recti extraocular muscles within the orbit. This study characterized the fine structure of the human medial rectus muscle pulley. METHODS: Human medial rectus muscle pulley tissue was dissected at autopsy, immersed in aldehyde fixative solution, and processed for and examined with light and electron microscopy. RESULTS: Pulley structure were located within posterior Tenon's fascia, closely surrounding the medial rectus muscle. Pulleys were comprised of a dense collagen matrix with alternating bands of collagen fibers precisely arranged at right angles to one another. This three-dimensional organization most likely confers high tensile strength to the pulley. Elastin fibrils were interspersed in the collagen matrix. Fibroblasts and mast cells were scattered throughout the relatively acellular and avascular collagen latticework. Connective tissue and smooth muscle bundles suspended the pulley from the periorbita. Smooth muscle was distributed in small, discrete bundles attached deeply into the dense pulley tissue. CONCLUSIONS: Fine structural observations confirm the existence and substantial structure of a pulley system in association with the medial rectus extraocular muscle. The presence of pulleys must be considered in models of the oculomotor plant. The cytoarchitecture and placement of pulleys suggest that they are internally rigid structures and are consistent with the idea that they determine functional origins for the extraocular muscles. However, the nature of the connective tissue-smooth muscle struts suspending the pulley system to the orbit supports the notion that the pulley position, and thus the vector force of the eye muscles, may be adjustable.

Biomechanical Phenomena↗

Fetal responses to maternal and fetal methamphetamine administration in sheep.

OBJECTIVES: The current study was designed to test the hypothesis that maternally administered methamphetamine decreases fetal PaO2 by reducing uterine blood flow and to determine the cardiovascular and blood gas responses to varying doses of methamphetamine given both to the fetus and the mother. STUDY DESIGN: Nine near-term pregnant sheep were surgically instrumented to measure maternal and fetal blood pressure and heart rate and uterine and umbilical blood flow. Fetal blood gases and pH were determined before and after each dose of methamphetamine. Methamphetamine was administered as intravenous bolus injections (30 to 35 minutes separating administration of each dose) into the maternal femoral vein in increasing doses of 0.03, 0.1, 0.3, and 1.0 mg/kg and on a separate days to the fetus into the hind limb vein as doses of 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg estimated fetal weight. RESULTS: Maternal methamphetamine administration produced a dose-related increase in maternal and fetal blood pressure and uterine vascular resistance, whereas uterine blood flow decreased in a dose-related fashion. Umbilical blood flow tended to increase slightly, but this did not reach significance. Fetal PaO2 decreased significantly, whereas fetal pH decreased only modestly. Direct fetal administration of methamphetamine produced dose-related increases in fetal blood pressure and umbilical blood flow and a significant decrease in fetal pH but no change in fetal PaO2. CONCLUSIONS: The fetal PaO2 decrease observed after maternal administration of methamphetamine appears to be a result of decreased uteroplacental perfusion, whereas the observed changes in fetal blood pressure and fetal pH appear to be a result of the direct action of methamphetamine on the fetus.

Animals↗

Visual system electrodiagnosis in neurologic disease of childhood.

Electrodiagnostic examination of the visual system includes visual evoked potentials and electroretinography. These tests can be applied to all ages. Pitfalls in the clinical ophthalmologic examination of children, such as optic nerve pallor and pigmentary retinopathy, can be clarified by these tests. Investigation of neurodegenerative disease may be directed to the most likely defect by results of visual evoked potential testing and electroretinography. The child who is unable to meaningfully communicate sensory experience can be objectively evaluated by these studies. Familiarity with the applications and limitations of these tests will allow the examiner to choose the appropriate setting and time to apply each of them.

Brain Diseases↗

Botulinum A toxin stimulates neurite branching in nerve-muscle cocultures.

In addition to skeletal muscle paralysis, type A botulinum toxin commonly causes sprouting of motor axons in various experimental whole-animal systems. The use of type A botulinum toxin in clinical treatment of muscle spasm disorders is becoming increasingly popular. The eventual, unwanted return of involuntary activity in the treated muscles may be a consequence of such axon sprouting. We have developed a coculture model allowing the quantification of botulinum toxin-induced sprouting that shows promise for future studies on its mechanism and control. Chick embryo ciliary ganglion motor neurons were cocultured with chick leg muscle cells. The presence of type A botulinum toxin in the coculture medium was correlated with significantly increased branching frequency of neurites. Toxin-increased branching frequency occurred even when the neurons and muscle cells were separated from each other on the culture dishes, suggesting a presynaptic effect of toxin. Cocultures incubated in the presence of curare, a post-synaptic blocker, had control levels of neurite branching, ruling out the possibility that simple synaptic blockade causes sprouting but again supporting the hypothesis of a pre-synaptic activity of botulinum toxin.

Animals↗

Aberrant reinnervation of facial musculature in a subhuman primate: a correlative analysis of eyelid kinematics, muscle synkinesis, and motoneuron localization.

A macaque monkey with a preexisting facial nerve injury showed a synkinesis of perioral muscles with blinking and thus provided a serendipitous model for a multiphasic analysis of this common neurologic syndrome. The amplitude of the paretic eyelid in spontaneous and air-puff-induced blinks was about one-third that of the normal eyelid. Despite the blink hypometria, induced blink durations remained matched for the two lids. EMG confirmed co-contraction of the zygomaticus and orbicularis oculi muscles on the affected side during blinking, with silence of the zygomaticus on the normal side. Neuroanatomic investigation showed that, on the affected side, some zygomaticus motoneurons were in the somatotopically correct nuclear subdivisions but that the majority were in the dorsal subdivision, which normally innervates the orbicularis oculi. This study supports the contention that some orbicularis oculi motoneurons are incorrectly rerouted to supply the perioral musculature following recovery from a peripheral seventh-nerve injury. This same pattern of relative weakness in eyelid muscles and the stereotyped co-contraction of lid and perioral muscles with blinking occurs in humans, suggesting that aberrant reinnervation may be the mechanism for this clinical phenomenon.

Animals↗

Conjugacy of spontaneous blinks in man: eyelid kinematics exhibit bilateral symmetry.

PURPOSE: To provide a quantitative description of the conjugacy of human eyelid movements during spontaneous blinks. METHODS: Eyelid movements occurring during spontaneous blinks were recorded bilaterally using a modification of the electromagnetic search coil technique. In off-line analyses, covariation of amplitude, peak velocity, and duration of blink down phases were determined for the two eyelids. Interocular differences in the timing of blink onset and offset, and time to peak velocity, also were evaluated. RESULTS: Human blink motor control systems act to link tightly the spatial and temporal characteristics of movements of the two eyelids. Data show that human spontaneous blinks are conjugate. Analysis of interocular covariation of blink amplitude, peak velocity, and duration yielded linear functions with high correlation coefficients. Interocular comparison of eyelid movement durations during blinks showed a particularly high correlation. There were negligible interocular differences in blink down-phase onset time, termination time, and time to peak velocity. A small percentage of blinks exhibited interocular differences in amplitude and peak velocity of > 20%; however, even in these cases, blink duration remained tightly linked. CONCLUSION: Spatial and temporal properties of eyelid movements occurring during spontaneous blinks are conjugate. These data support the hypothesis that a bilateral gating mechanism regulates blink duration. Elements downstream from the gate may differentially and unilaterally alter blink amplitude and peak velocity, but the duration of blinks remains time-locked for the two eyelids.

Adult↗

Reproducibility of postural changes in intraocular pressure with the Tono-Pen and Pulsair tonometers.

Reproducibility of measurements of postural changes in intraocular pressure was determined by using the Tono-Pen (Mentor O & O, Inc., Norwell, Massachusetts) and Pulsair (Keeler Instruments, Inc., Broomhall, Pennsylvania) tonometers. Thirty subjects had three repeated sitting and reclining measurements performed on three separate visit days. Reproducibility coefficients of 3.3% for the Tono-Pen and 6.3% for the Pulsair were obtained for the within-visit postural change measurements. Across-visit reproducibility coefficients were 7.9% and 26.2% for the Tono-Pen and Pulsair, respectively. The estimated standard deviations for both the within-visit and across-visit postural change measurements were high for both instruments. These results indicate poor reproducibility of measurements of postural changes in intraocular pressure.

Adult↗

Quantitative analysis of eyelid movement metrics reveals the highly stereotyped nature of monkey blinks.

Blink movement metrics were studied in three alert cynomolgus monkeys using electromagnetic search coils attached to the eyelids bilaterally. Monkey blinks averaged approximately 24 degrees. Down-phase peak velocities were approximately twice those of the corresponding up phases. Most blinks were symmetrical with close temporal linkage of onset and offset between the two eyelids. Monkey blinks exhibited higher peak velocities and shorter durations than have been previously described for similar amplitude movements in humans. Peak velocity vs. amplitude plots were linear and non-saturating within a 45 degrees range for both up and down phases. The relationship between blink peak velocity and average velocity was linear with a slope of approximately 2.0. These values were very similar to those obtained by others, not only for blinks, but also for saccadic eye and ballistic limb movements. Down-phase amplitude-duration behavior could be best described by a linear function with slope < 0.7, while amplitude-duration slope of up phases was best described by a second-order polynomial. Unlike saccadic eye movements, larger amplitude blinks are obtained primarily via increases in peak velocity rather than through extension of blink duration. These data provide mathematical descriptions of monkey blink behavior that indicate the stereotypical nature of blinks. This will serve as a normative data base with which to better understand the neural processing that goes into blinks and will allow the assessment of eyelid movement disorders and evaluation of potential treatments of these disorders.

Animals↗

Types and time course of the alterations induced in monkey blink movements by botulinum toxin.

The alterations induced in eyelid movement metrics subsequent to unilateral injections of botulinum toxin type A into the orbicularis oculi muscle were studied in chronic alert monkeys using the search coil technique. Botulinum toxin caused rapid paralysis of blinks in the treated eyelid. The amplitude and peak velocity of blinks generated by this eyelid remained at or below 20% of that of the fellow, untreated eyelid for 10-20 days. Blink amplitude gain increased linearly thereafter, attaining control values by 40-60 days after injection. Recovery of blink peak velocity was slower. The adaptive alterations in blink duration that were observed during the acute phase of toxin paralysis suggest that the mechanisms responsible for blink reflex plasticity may produce bilateral adjustments in eyelid function. Taken together, these data establish a quantitative data base that can be exploited in order to: (1) better understand the neural adaptive mechanisms that operate during eyelid movements and (2) allow quantitative comparisons between current treatment protocols that employ botulinum toxin and protocols that may lead to improvements in the treatment of chronic eyelid spasm (blepharospasm).

Animals↗

Maternal and fetal cardiovascular responses to methamphetamine in the pregnant sheep.

OBJECTIVES: Our purpose was to evaluate the maternal and fetal cardiovascular effects of maternally administered methamphetamine and to determine the extent of placental transfer. STUDY DESIGN: Seven near-term pregnant sheep were surgically instrumented to measure maternal and fetal blood pressure and heart rate, cardiac output, uterine flow, and umbilical flow. A single dose of methamphetamine 1 mg/kg was administered as a bolus to study maternal and fetal cardiovascular responses and placental transfer. RESULTS: Maternal administration of methamphetamine caused increases in maternal blood pressure, heart rate, cardiac output, and systemic vascular resistance and decreased uterine blood flow. Peak maternal changes occurred within 10 minutes after methamphetamine administration and were near baseline by 180 minutes. Fetal blood pressure increased and returned slowly to baseline by 2 hours. After an initial decrease fetal heart rate increased above baseline values over the next 2 hours. Umbilical blood flow also decreased initially and then increased slightly. Fetal pH and PO2 tended to decrease. Maternal and fetal methamphetamine levels reached a maximum of 2.9 and 1.9 micrograms/ml, respectively. Rapid and significant placental transfer, delayed excretion into the amniotic fluid, and slow elimination from the maternal and fetal circulation were demonstrated. CONCLUSION: Methamphetamine readily crosses the ovine placenta, producing significant and long-lasting maternal and fetal cardiovascular effects, which may have long-term consequences, especially if administered repetitively.

Amniotic Fluid↗

Cytogenetic damage and tumor incidence in mouse skin after single, topical applications of 7,12-dimethylbenz[a]anthracene.

Micronucleus induction, chromosomal damage and aneuploidy were evaluated in whole skin keratinocyte cultures derived from HRA/Skh mice after single in vivo applications of 0.256, 2.56 and 25.6 micrograms (1, 10 and 100 nmoles) of the carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA). These genotoxicity end-points were compared with papilloma and carcinoma occurrence at the same dose levels of carcinogen. While the lower 2 doses of DMBA significantly increased the incidence of micronuclei and other chromosomal anomalies in keratinocytes, the two highest doses resulted in a significantly increased papilloma yield (0.297 and 3.895 papillomas/mouse) and incidence (24.3 and 100%). Carcinomas appeared only at the highest dose (0.125 carcinomas/mouse; 5% incidence). Neither papillomas nor carcinomas occurred in solvent-treated control mice. None of the three applied doses induced aneuploidy under conditions leading to an increase in tumors and/or chromosomal damage.

9,10-Dimethyl-1,2-benzanthracene↗

Cranial injury from unsuspected penetrating orbital trauma: a review of five cases.

Penetrating orbital-cranial injury is potentially life threatening. The history of the trauma and ophthalmologic examination may be misleadingly innocent; serious injury may be overlooked. We present five cases of orbital injury in which the diagnosis of intracranial extension was not obvious at the time of initial examination. A thorough history and physical examination should be performed on all patients, even those with apparently trivial injuries. Intracranial extension should be considered in any case where the injury was caused by an instrument small enough to enter the orbit. The threshold for obtaining a coronal CT scan of the orbits should be lowered, since this is the best way to detect an orbital roof fracture.

Adolescent↗

Type-specific changes in fiber morphometry following denervation of canine extraocular muscle.

To investigate the changes that occur in extraocular muscle morphometry following denervation, 12 beagles were subjected to intracranial section of the left oculomotor nerve. The inferior and medial rectus muscles were removed from both orbits of four dogs killed at each 4-week postoperative interval. Fiber diameters and fiber-type ratios of denervated muscles were compared with those from paired muscles in the normal orbit. We found significant, persistent atrophy of the singly innervated fibers in both the global and orbital layers of denervated extraocular muscle. The multiinnervated fibers were predominantly spared from denervation atrophy. We also found a significant increase in the proportion of multiinnervated fibers in the orbital layer only. These results suggest a relative neurotrophic independence of multiinnervated fibers in extraocular muscle.

Animals↗

Tumorigenicity of cyclopenta[a]phenanthrene derivatives and micronucleus induction in mouse skin.

The most potent carcinogen of the cyclopenta[a]phenanthrene series, 15, 16-dihydro-11-methylcyclopenta[a]phenanthren-17-one and its non-carcinogenic, unmethylated parent compound, were compared for their abilities to induce micronuclei in epidermal keratinocytes after application onto the dorsal skin of Skh/HR-1 hairless mice. Although both substances were shown to be mutagenic in vitro, only the 11-methyl derivative has been proven to initiate cancer in TO and Sencar mouse strains. In the present study, only the 11-methyl derivative was active as a cancer initiator in Skh/HR-1 mice. For studying micronucleus induction, a preliminary experiment was conducted to establish doses of both chemicals that allowed cell survival. Subsequently, micronucleus induction in epidermal keratinocytes was shown to agree with the cancer-initiating potential of the two compounds. Only the carcinogenic derivative induced a statistically significant increase in micronuclei, over the range 10-100 nmol. This is considerably lower than the dose of approximately 1600 nmol commonly used to initiate skin cancer in mice, but is comparable to the active dose range for skin micronucleus induction by benzo[a]pyrene, a chemical of equivalent carcinogenic potency.

Animals↗

Skin carcinomas and micronucleus induction in epidermal keratinocytes following 12-O-tetradecanoylphorbol-13-acetate and mezerein treatment.

Phorbol esters are chemical compounds which have the ability to promote carcinogenesis in the skin of mice. In the HRA/Skh mouse strain, an initiation-promotion assay substantiated evidence that mezerein acts as a complete promoter. Complete promotion with 9.0 nmol mezerein induced a total of 53 papillomas in 28 mice within 40 weeks, while 1.5 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA), using the same application regime, resulted in a total of 298 papillomas in 58 mice. However, 7.6% of the papillomas in the mezerein group progressed to carcinomas, compared with 0.7% in the TPA group. Approximately the same molar concentrations of TPA and mezerein induced a dose-dependent and reproducible increase in micronuclei in supra-basal cells derived from the epidermis of treated mice. In contrast, the latter compound was less toxic to these cells and induced higher numbers of micronuclei at the higher concentrations.

Animals↗