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Biomedical subjects

D C Rice

Publications and source records attributed to D C Rice.

At least 55 records · Page 3Linked to original sources

Increased sensitivity in objective monitoring of tissue expansion.

The end point for incremental filling of any tissue expander normally may reliably be assessed using subjective parameters, especially pain, as a guideline. However, in unusual circumstances, such as within denervated areas, the presence of marginal skin circulation, or if rapid expansion is required, an objective monitor may be beneficial to ensure safer expansion. We have previously examined the role of serial measurement of transcutaneous oxygen in this regard. In an effort to refine this sometimes cumbersome approach, a comparison using laser Doppler flowmetry as well has been undertaken in 13 consecutive patients. Both monitoring devices demonstrated a progressive impediment to blood flow with increased expansion. At the pain threshold, both techniques recorded values consistent with adequate skin circulation, thereby proving in general the relative safety of subjective evaluation during the usual course of tissue expansion. Greater sensitivity was noted for the laser Doppler as a monitor, though, via the recording of earlier changes in flow characteristics and more rapid identification of critical thresholds for nonviability. From a more practical standpoint, immediate application without a period for equilibration is another major asset of laser Doppler flowmetry as a system for objective monitoring.

Adolescent↗

Biomechanics of ocular pneumoplethysmography.

A mathematical analysis of ocular pneumoplethysmography is presented, based on the physiological, anatomical, and biomechanical properties of the eye. Ocular pneumoplethysmography is a clinical procedure involving elevation of intraocular pressure, by application of a suction cup to the sclera, to a level that exceeds ophthalmic artery systolic pressure. As decay in intraocular pressure is allowed, return of retinal artery pulsations indicates ophthalmic artery systolic pressure. We obtain a quantitative relationship between increase in intraocular pressure and applied vacuum, and compare the theoretical predictions with experiments on rabbits in which a variable descending vacuum was applied to bilateral scleral eyecups. The bilateral intraocular pressures were simultaneously recorded from cannulae in the respective vitreous bodies, and the pressures at which return of ocular pulsations were observed were correlated with the scleral vacuums. Regression lines were calculated for three serial determinations in each animal, with two groups of animals distinguished by the inner diameter of the eyecups used. The theoretical results indicate that the relationship between intraocular pressure increase and applied vacuum is independent of Young's modulus, and depends primarily on the ratio of the diameter of the vacuum cup to the diameter of the eye.

Animals↗

Comparison of the contact neodymium:YAG and carbon dioxide lasers for skin deepithelialization.

The application of laserbrasion by the carbon dioxide (CO2) laser for skin deepithelialization previously has been proven efficacious in numerous clinical experiences. This study in adult Sprague-Dawley rats was designed to compare those known effects of the CO2 laser with the contact neodymium:yttrium-aluminum-garnet (Nd:YAG) laser for skin deepithelialization, since tactile feedback from the handpiece of the latter is a theoretical advantage. This proved that although the contact Nd:YAG laser does have the capability to achieve skin deepithelialization, when compared with more conventional methods, it is laboriously inefficient and therefore at present impractical.

Animals↗

Feasibility of skin deepithelialization using the contact neodymium-yttrium-aluminum-garnet laser.

In a manner similar to laserbrasion, the carbon dioxide (CO2) laser has a proven role for expediting skin deepithelialization, which is an essential component of many reconstructive procedures. However, the contact Neodymium-Yttrium-Aluminum-Garnet (Nd:YAG) laser has many additional attributes such as tactile feedback and less plume that theoretically offer an advantage over the CO2 laser for this adjunctive maneuver. In rat experimental models and clinical applications, removal of the epidermis necessary for skin deepithelialization may indeed be achieved using a rounded probe for vaporization with the contact Nd:YAG laser. Unfortunately, the length of time necessary for skin deepithelialization with the Nd:YAG laser exceeded even conventional methods, such that this role with the present technology, although possible, is inefficient and impractical.

Aluminum Silicates↗

Exposure to methyl mercury from birth to adulthood impairs high-frequency hearing in monkeys.

Hearing deficits are a frequent consequence of both developmental and adult methyl mercury exposure in humans. However, a detailed characterization of these deficits has not been performed in either humans or animals. Cynomolgus monkeys (Macaca fascicularis) were dosed from birth to 7 years of age with 50 micrograms/kg/day of mercury as methyl mercuric chloride. Steady-state blood mercury levels during dosing were 0.6-0.9 ppm. When monkeys were 14 years old, pure tone detection thresholds were determined by a psychophysical procedure. Control monkeys exhibited thresholds at frequencies between 125 and 31,500 Hz comparable to previously published values for macaques. One methyl mercury-treated monkey exhibited normal detection thresholds at all frequencies. Three treated monkeys were impaired at the second highest frequency tested (25,000 Hz) and therefore were not tested at 31,500 Hz. The fifth treated monkey displayed severely elevated thresholds at middle frequencies (10,000-12,500 Hz), precluding testing at higher frequencies. These results indicate a selective high-frequency deficit in monkeys exposed to methyl mercury from birth to adulthood and not exposed to methyl mercury in the 7 intervening years before auditory testing. These findings extend previous results in this group of monkeys in which deficits in spatial and temporal visual function were observed.

Animals↗

Laser deepithelialization of the transverse rectus abdominis musculocutaneous flap.

Total or partial skin deepithelialization of the transverse rectus abdominis musculocutaneous (TRAM) flap is an integral component of this technique for achieving a successful breast reconstruction. In a manner similar to dermabrasion, the carbon dioxide laser in a defocused mode permits precise removal by vaporization of the epidermis and outer dermis. The extended application of this method for deepithelializing the TRAM flap is simple, rapid, and safe. Because a portion of the dermis always remains intact, another inherent advantage of this method is preservation of the subdermal vascular plexus that may be important for maintaining any precarious flap perfusion.

Abdominal Muscles↗

Lead exposure during different developmental periods produces different effects on FI performance in monkeys tested as juveniles and adults.

Monkeys (Macaca fascicularis) were dosed with 0 or 1500 micrograms/kg/day of lead as lead acetate according to one of four regimens: Group 1, vehicle continuously from birth; Group 2, lead continuously from birth; Group 3, lead from birth to 400 days of age and vehicle thereafter; Group 4, vehicle from birth to 300 days of age and lead thereafter. Blood lead values of the three treated groups were approximately 20-35 micrograms/dl, depending on age. Performance on a multiple fixed interval-fixed ratio (mult FI-FR) schedule of reinforcement was assessed when monkeys were three years of age, and again at 7-8 years of age following exposure to other behavioral tasks. Results of the first assessment were largely negative, with lead-treated monkeys failing to exhibit the rate increases on the FI observed in previous groups of monkeys tested at the same age. The second assessment revealed increased run rates and decreased average IRTs on the FI in all three treated groups. Effects on the FR component were minimal and transient during both assessment periods, which is consistent with previous results. Monkeys in previous studies had a history of tasks with trials procedures, in which every correct response was reinforced, before being tested on the mult FI-FR. The monkeys in the present study had no such history before the first assessment, but extensive exposure to trials procedures between the first and second assessment. It may be that the negative results of the first assessment and positive results of the second are the result of an interaction of lead with such a behavioral history. This suggestion is especially compelling in view of the results from Group 3, dosed only during infancy. These monkeys were unaffected during the first assessment, performed two years after cessation of dosing, but performed differently from controls on the second assessment, performed 5-6 years after cessation of dosing. This finding, combined with data from previous experiments, suggests that the greater total dose of lead accumulated by Groups 2 and 4 between the first and second assessment is not an explanation for the difference in results. These results also indicate that exposure to lead during infancy is not necessary for FI performance to be affected, and that exposure only during infancy is sufficient to produce effects.

Aging↗

Effects of pre- plus postnatal exposure to methylmercury in the monkey on fixed interval and discrimination reversal performance.

Female monkeys were dosed with 0, 10, 25 or 50 micrograms/kg/day of mercury as methylmercuric chloride. When blood levels reached equilibrium, females were bred to untreated males. A total of 5, 1, 2, and 5 live infants were born in the four dose groups, respectively. Infants were separated from their mothers at birth, and dosed with the same dose their mothers had received. Maternal blood mercury levels averaged 0.33, 0.78, or 1.41 ppm for the three dosed groups respectively. Infant blood mercury levels averaged 0.46, 0.93, or 2.66 ppm at birth, and decreased slowly to steady state levels of 0.20, 0.25, or 0.60 ppm. Behavior was assessed during infancy on a nonspatial discrimination reversal task and fixed interval performance, and when monkeys were juveniles on a series of nonspatial discrimination reversal tasks. During infancy monkeys were tested 7 days per week, 16-21 hr per day in a home-cage environment. As juveniles, they were tested five days per week in a standard operant test environment. For the discrimination reversal tasks, there were no strong indications of differences between treated and control monkeys either as infants or juveniles. Treated monkeys tended to perform transiently better than controls when first introduced to the task both as infants and juveniles. On the Fl, treated monkeys received more reinforcements, and had shorter pauses and lower quarter-life values than control monkeys. Analysis of feeding behavior over the session during infancy revealed marginally longer periods of feeding in methylmercury-treated infants. These results suggest that pre-plus postnatal exposure to methylmercury did not result in gross intellectual impairment in these monkeys, but may have interfered with temporal discrimination.

Animals↗

Effect of lead during different developmental periods in the monkey on concurrent discrimination performance.

A total of 52 monkeys (Macaca fascicularis) were dosed orally with vehicle or 1.5 mg/kg/day of lead according to one of four dosing regimens (13 monkeys/group): Group 1, vehicle only; Group 2, dosed with lead continuously from birth; Group 3, dosed with lead from birth to 400 days of age and vehicle thereafter; Group 4, dosed with vehicle from birth to 300 days of age and lead thereafter. Blood lead concentrations averaged 3-6 micrograms/dl when monkeys were not dosed with lead, 32-36 micrograms/dl when being dosed with lead and having access to infant formula, and 19-26 micrograms/dl when being dosed with lead after weaning from infant formula. When monkeys were 8-9 years old, they were tested on two sets of concurrent discrimination tasks, each consisting of 6 stimulus pairs. Group 2 required more sessions on Task 1 for 5 of the 6 pairs to reach a criterion of 90% correct, while Groups 3 and 4 required more or marginally more sessions on 4 of the 6 pairs. On Task 2, Group 2 required more sessions to reach criterion for most pairs, Group 4 was marginally impaired, and Group 3 was unimpaired. All three treated groups made more perseverative errors than controls on Task 1, but not on Task 2. There were no differences between groups for response latency or position bias. This extends previous research with these monkeys, in which impairment was observed on spatial and nonspatial discrimination reversal, and spatial delayed alternation.

Animals↗

Effects of chronic caffeine consumption in pregnant monkeys (Macaca fascicularis) on blood and urine clinical chemistry parameters.

Pregnancy requires a variety of physiological adaptations to create an environment for the optimal development of the fetus. The widespread consumption of the methylxanthines especially caffeine and to a lesser extent theophylline by pregnant women suggests that it is important to determine whether these methylxanthines may influence maternal physiology during pregnancy. Forty female monkeys (Macaca fascicularis), randomly divided into three groups, were exposed to caffeine in their drinking water (0, 0.15, or 0.35 mg/ml) before, during, and after pregnancy. This exposure resulted in a dose-related increase in reproductive failure in the form of stillbirths, miscarriages, and decreased maternal weight gain. Blood and 24-hr urine samples were collected every 2 weeks for clinical chemistry analysis. There were a number of both pregnancy-related changes and treatment-related effects on the clinical chemistry measures. As expected, serum cholesterol and triglyceride levels declined during pregnancy for all dose groups but there were no treatment-related effects. Serum and urine creatinine levels were increased in both treated groups. Serum glucose levels, which usually decline during pregnancy, remained elevated in the high-dose group. Serum estrogen levels in the high-dose groups were depressed compared to those of the other two groups. These changes indicate that elevated serum levels of caffeine and its metabolites, particularly theophylline, may influence maternal physiology during pregnancy in the monkey.

Animals↗

Somatic development of the infant monkey following in utero exposure to caffeine.

Caffeine has been associated with a number of reproductive and developmental effects in animals and humans. In an effort to characterize the potential effects of caffeine on the developing infant, 40 adult female monkeys (Macaca fascicularis) were randomly divided into three groups and exposed at 0, 0.15, and 0.35 mg/ml (equivalent to 0, 10-15, and 25-30 mg/kg/day, respectively) of caffeine via their drinking water, before, during, and after pregnancy. Maternal blood and milk samples were collected following parturition. Infants were separated from their mothers within 12 hr of birth and were reared in a primate nursery. Blood samples were collected during the first week of life, and body weight, somatic measurements, and food consumption data were collected throughout the first 3 years. Maternal blood and milk concentrations and infant blood concentrations of caffeine and theophylline (the major blood metabolite of caffeine in the monkey) were similar to one another. Infant half-life of these methylxanthines was longer than that of the adult but not as long as that observed in human infants. Body weights and somatic measurements of male infants were significantly reduced over the first 30 days, as were a number of initial somatic measurements in both male and female infants. These deficits were not evident after 1 year of age. There were no treatment-related effects on infant tooth eruption or milk consumption. Results from this study support previously published results from this group of monkeys as well as studies by other researchers in rodents indicating that caffeine consumption during pregnancy can alter infant somatic development.

Animals↗

Sensitive periods for lead-induced behavioral impairment (nonspatial discrimination reversal) in monkeys.

A total of 52 nursery-reared monkeys (Macaca fascicularis) were dosed orally with 1.5 mg/kg/day of lead on one of four dosing regimens (13 monkeys/group): Group 1, vehicle only; Group 2, dosed with lead continuously from birth; Group 3, dosed with lead from birth to 400 days of age and vehicle thereafter; and Group 4, dosed with vehicle from birth to 300 days of age and lead thereafter. This dosing regimen allowed evaluation of differential infant vulnerability as well as reversibility of the behavioral toxicity of lead. Blood lead concentrations averaged 3-6 micrograms/dl when monkeys were not being exposed to lead, 32-36 micrograms/dl when being dosed with lead and having access to infant formula, and 19-26 micrograms/dl during lead exposure after weaning from infant formula. When monkeys were 5-6 years old, they were tested on a series of nonspatial discrimination reversal tasks: form, form with irrelevant color cues, color with irrelevant form cues, and alternating form and color. Group 2 exhibited the greatest degree of impairment compared to controls. Group 4 also exhibited impaired performance, although less marked than that of Group 2. Group 3 was not impaired on this series of tasks. These results confirm findings observed in other monkeys exposed continuously to lead and suggest that while exposure beginning after infancy produces impairment, exposure during infancy as well exacerbates the effect.

Aging↗

Effects of developmental exposure to methyl mercury on spatial and temporal visual function in monkeys.

Detailed characterization of several aspects of visual function was made in two groups of monkeys exposed developmentally to methyl mercury. One group of monkeys (Macaca fascicularis) was dosed from birth onward with 50 micrograms/kg/day of mercury as methyl mercury. Another group was exposed in utero by dosing the mother with 10, 25, or 50 micrograms/kg/day of mercury as methyl mercury, and postnatally until 4.0-4.5 years of age with the same dose the mother had received. Spatial and temporal visual function was tested in both groups. Spatial visual deficits observed in the group dosed beginning postnatally were reported previously (Rice and Gilbert, 1982, Science, 216, 759-761). Monkeys exposed in utero plus postnatally exhibited impaired high- and low-luminance spatial vision. They also exhibited deficits in low-frequency high-luminance temporal vision, while low-luminance temporal vision was superior to that of control monkeys. Monkeys in which exposure began at birth displayed superior low-luminance temporal vision, while high-luminance temporal vision was not impaired. These effects were observed in the absence of constriction of visual fields. These data suggest that the pattern of visual deficits produced by developmental exposure to methyl mercury may be different from that in the adult, and that the developing visual system may be able to remodel as a result of early insult by a neurotoxic agent.

Animals↗

Lack of sensitive period for lead-induced behavioral impairment on a spatial delayed alternation task in monkeys.

A total of 52 monkeys (Macaca fascicularis) were dosed orally with vehicle or 1.5 mg/kg/day of lead on one of four dosing regimens (13 monkeys/group): vehicle only; dosed with lead from birth onward; dosed with lead from birth to 400 days of age and vehicle thereafter; dosed with vehicle from birth to 300 days of age and lead thereafter. Blood lead concentrations averaged 3-6 micrograms/dl when monkeys were not being dosed with lead, 32-36 micrograms/dl when being dosed with lead and having access to infant formula, and 19-26 micrograms/dl when being dosed with lead after weaning from infant formula. When monkeys were 6-7 years old, they were tested on a spatial delayed alternation task. The task required the monkey to alternate responses between two push buttons. The initial delay was 0.10 sec and was increased in steps to 15 sec by the end of the experiment. All three treated groups were impaired to approximately an equal degree. Deficits were observed in the initial training procedure, and at the longer delay values. These results suggest that there is not an early critical period for lead-induced impairment on this task and that exposure only during infancy results in impairment comparable to ongoing exposure beginning at birth. These results are in contrast to previous findings on a series of nonspatial discrimination reversal tasks, in which the group exposed early in life only was unimpaired, while the group exposed beginning after infancy was less impaired that the group exposed continuously from birth.

Age Factors↗

Lead-induced behavioral impairment on a spatial discrimination reversal task in monkeys exposed during different periods of development.

A total of 52 monkeys (Macaca fascicularis) were dosed orally with vehicle or 1.5 mg/kg/day of lead on one of four dosing regimens (13 monkeys/group): Group 1, vehicle only; Group 2, dosed with lead from birth onward; Group 3, dosed with lead from birth to 400 days of age and vehicle thereafter; Group 4, dosed with vehicle from birth to 300 days of age and lead thereafter. Blood lead concentrations averaged 3-6 micrograms/dl when monkeys were not being dosed with lead, 32-36 micrograms/dl when being dosed with lead and having access to infant formula, and 19-26 micrograms/dl when being dosed with lead after weaning from infant formula. When monkeys were 7-8 years old, they were tested on three spatial discrimination reversal tasks: no irrelevant cues, irrelevant form cues, and irrelevant form and color cues. Fifteen reversals were run for each task. Only Group 2 was impaired in the absence of irrelevant cues, while all three treated groups were impaired in the presence of irrelevant cues. These results are in contrast to results from a series of nonspatial discrimination reversal tasks in these monkeys in which Groups 2 and 4 were impaired and Group 3 was unimpaired. The present results are in agreement with results from another spatial task, delayed alternation, in which all three treated groups were impaired.

Aging↗

In utero fetal surgery using a milliwatt carbon dioxide laser.

In utero surgery represents a future new frontier with unknown possibilities for medical intervention. Since the presently available microsurgery instruments are too cumbersome or indelicate, low-energy carbon dioxide lasers have been investigated as a tool that holds promise as a fetal scalpel and hemastatic device. Preliminary results demonstrate that continued investigation is necessary to limit the zone of tissue destruction in these most diminutive patients.

Animals↗

Effects of chronic developmental lead exposure on monkey neuroanatomy: visual system.

The effects of lead on specific areas of the visual system were examined in two groups of monkeys (Macaca fascicularis). The first group (N = 3) received 2000 micrograms Pb/kg/day from infancy onward, while the second group (N = 4) received 25 micrograms Pb/kg/day from birth onward. Monkeys were killed at approximately 6 years of age. Areas of the visual system, including optic nerve, lateral geniculate nucleus, and primary area V1 and one visual projection area V2, were examined by a combination of light and electron microscopy and Golgi impregnation. No effect of lead on optic nerve was identified, nor were there consistent differences in the lateral geniculate nucleus. Within areas V1 and V2, the neuronal volume density was significantly reduced in the high dose compared to the low dose group. Moreover, analysis of the dendritic arborization by Golgi analysis revealed a relative decrease in the number of arborizations among pyramidal neurons in both areas V1 and V2. These data suggest that lead exposure beginning during the early postnatal period may result in changes in cytoarchitecture in visual areas V1 and V2.

Animals↗

Pharmacokinetics of methylmercury in the blood of monkeys (Macaca fascicularis).

Statistical analysis of the blood mercury profiles of groups of two and four adult female cynomolgus monkeys (Macaca fascicularis) given single oral doses of 500 micrograms and 50 microCi (25.3 micrograms) methylmercury/kg body wt, respectively, indicates that a two-compartment model best describes the absorption and elimination of methylmercury in blood. Absorption was largely complete within 6 hr, and the half-time of methylmercury during the terminal elimination phase ranged from 10 to 15 days. In addition, three groups of five adult female cynomolgus monkeys were dosed with methylmercury every Monday, Wednesday, and Friday for periods up to 2 years at effective doses of 10, 25, or 50 micrograms methylmercury/kg body wt/day. The average blood levels at steady state were estimated to be 0.27 +/- 0.02, 0.69 +/- 0.03, and 1.51 +/- 0.08 ppm, respectively, with average time taken to achieve 95% of the steady-state blood level being about 92 days. The steady-state blood levels obtained via extrapolation of the results from the two single-dose experiments were significantly different from those actually achieved, indicating that the average steady-state blood levels under chronic dosing conditions may not be accurately estimated on the basis of short-term experiments. The data were also used to examine the impact of different dosing intervals on variation in blood mercury levels.

Animals↗