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Biomedical subjects

R S Baker

Publications and source records attributed to R S Baker.

At least 19 recordsLinked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

Prenatal morphogenesis of primate extraocular muscle: neuromuscular junction formation and fiber type differentiation.

Extraocular muscle represents a distinctive class among mammalian skeletal musculature in exhibiting the full range of muscle fiber type variability found in vertebrate species. To better understand the basis for the unique structural/functional diversity of extraocular muscle, the ontogeny of lateral rectus muscles was studied in Macaca nemestrina fetuses of 62-156 days gestation using light and electron microscopy. At E62, myotubes and myofibers are evident, but fiber-type differentiation has not yet occurred and neuromuscular junctions are primitive. By E92, presumptive singly and multiply innervated fiber types could be distinguished on the basis of myofibril delineation. Like other skeletal muscles, extraocular myogenesis proceeds through at least two generations of myofibers. All primary and secondary myofibers were generated and were maturing by E121. The phylogenetically "old" global multiply innervated fiber type was the first to attain adult form. This was followed by maturation of global layer singly innervated fiber types, which are developed by E156, except for attainment of definitive size and mitochondrial content. Orbital layer fiber types, particularly the orbital singly innervated fiber, are the last to mature. Neuromuscular junction maturation paralleled the changes observed during fiber-type differentiation. In summary, the sequential development of their constituent muscle fiber types may reflect the functional pressures the extraocular muscles are exposed to by maturing visual and visuomotor systems. In particular, ontogenic and phylogenic changes observed in the orbital singly innervated fiber type may have direct implications for the types, range, and precision of eye movements used by different species and at different gestational ages.

Animals↗
PubMed1991

Use of bioerodible polymers impregnated with mitomycin in glaucoma filtration surgery in rabbits.

A prospective, randomized, double-masked, and placebo-controlled study was performed to evaluate the effects of a localized and sustained release of mitomycin on the success of glaucoma filtration surgery in rabbits. A bioerodible polymer was used as the drug carrier. Full-thickness filtration surgeries were performed and data from 22 rabbits were collected. One eye received a polymer impregnated with mitomycin (0.02 mg or 0.06 mg), while the fellow eye received a drug-free polymer. Intraocular pressure, bleb survival, and postoperative complications were investigated. Intraocular pressures remained lower for a longer period of time (P less than 0.004) and filtration blebs lasted longer (P less than 0.05) in experimental eyes than in control eyes. Conjunctivitis and sectorial corneal haze occurred more frequently in eyes treated with the higher dosage mitomycin compared with control eyes. The use of mitomycin-C in a polymer delivery system appeared to promote the success of glaucoma filtration surgery in rabbits. With the lower dosage of mitomycin, clinically significant ocular toxicity was not noted.

Animals↗
PubMed1991

Evaluation of optic nerve sheath fenestration in pseudotumor cerebri using automated perimetry.

Evaluation of the efficacy of optic nerve sheath fenestration in pseudotumor cerebri has been hindered by a lack of quantitative indicators of visual function before and after treatment. Nine patients (14 eyes) were treated who had pseudotumor with optic nerve sheath fenestration, in whom automated perimetry was used as a major parameter in the decision to undertake surgery and in evaluating the results. Visual field results demonstrated significant improvement in this group of patients. Seven of 8 eyes with total loss less than 1500 dB had improvement or no further deterioration. Using results of the last preoperative examination as baseline, it was found that six of the eight had improvement over 150 dB. In one patient, a slight deterioration occurred postoperatively. Those eyes with total loss above 1500 dB demonstrated stabilization of fields postoperatively. Statistical analysis of total loss preoperatively and postoperatively for this group of patients demonstrated significant improvement for five of the six comparisons investigated. Average preoperative total loss and average postoperative total loss were not significantly different. Comparisons of results of the last preoperative examination to those of the first postoperative and most recent follow-up examinations, and evaluation of average total loss postoperatively showed significant improvement had occurred. Results of the first postoperative examination and those of the most recent follow-up examination showed significant improvement from the average preoperative total loss.

Adult↗
PubMed1991

The effects of topical mitomycin on glaucoma filtration surgery in rabbits.

A prospective, randomized, double-masked, and placebo controlled study was performed to examine the effects of topically applied mitomycin on the success of full thickness filtration surgery in 23 rabbits. Both eyes of each rabbit had surgery by the same surgeon. After surgery, the experimental eye received a single subconjunctival injection of mitomycin (0.2 mg), and 50 microliters of a 0.2 mg/cc solution of mitomycin topically four time daily. The fellow control eyes were treated with sterile water. The mean intraocular pressure reduction from baseline exhibited by the experimental eyes was greater than that observed for the control eyes. The difference in intraocular pressure reduction between the two groups was statistically significant from post-operative day three through day 21 (p less than .05). With survival analysis, fewer failures were noted in the experimental eyes compared to control eyes for each time period throughout the study (p less than .005). The experimental eyes also demonstrated a longer time to bleb failure although this difference did not achieve statistical significance (p less than .10). An additional five rabbits were treated with the experimental drop in one eye and sterile water in the fellow eye but underwent no surgery. No differences between eyes were noted with regard to intraocular pressure change or anterior segment pathology. These data demonstrated the efficacy of mitomycin in promoting filtration surgical success in rabbits.

Administration, Topical↗