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Biomedical subjects

D C Rice

Publications and source records attributed to D C Rice.

At least 73 records · Page 4Linked to original sources

Blood mercury concentrations following methyl mercury exposure in adult and infant monkeys.

Female monkeys (Macaca fascicularis) were dosed chronically with the equivalent of 10, 25, or 50 micrograms/kg/day methyl mercury until at least 90% of estimated blood equilibrium was reached and were then bred to untreated males. Infants were dosed with the same dose their mothers had received. An additional group of infants was dosed with 50 micrograms/kg/day beginning at birth. Infants exposed in utero were born with higher (1.7x) mercury levels than their mothers, but blood mercury levels of the offspring decreased to less than one-half that of the mothers. The steady-state blood levels of the group exposed postnatally were not different from steady-state levels of the group exposed in utero plus postnatally. When dosing was discontinued, the rate coefficient of elimination from blood did not differ between the adults (mothers) and the in utero plus postnatally exposed group, while that of the group exposed postnatally only was lower. There was no indication of a relationship in the rate of elimination for mother-infant pairs. These results suggest that the kinetics of methyl mercury in blood are complicated and may depend on the age of the individual when exposure begins.

Animals↗

Brain and tissue levels of mercury after chronic methylmercury exposure in the monkey.

Estimated half-lives of mercury following methylmercury exposure in humans are 52-93 d for whole body and 49-164 d for blood. In its most recent 1980 review, the World Health Organization concluded that there was no evidence to suggest that brain half-life differed from whole-body half-life. In the present study, female monkeys (Macaca fascicularis) were dosed for at least 1.7 yr with 10, 25, or 50 micrograms/kg.d of mercury as methylmercuric chloride. Dosing was discontinued, and blood half-life was determined to be about 14 d. Approximately 230 d after cessation of dosing, monkeys were sacrificed and organ and regional brain total mercury levels determined. One monkey that died while still being dosed had brain mercury levels three times higher than levels in blood. Theoretical calculations were performed assuming steady-state brain:blood ratios of 3, 5, or 10. Brain mercury levels were at least three orders of magnitude higher than those predicted by assuming the half-life in brain to be the same as that in blood. Estimated half-lives in brain were between 56 (brain:blood ratio of 3) and 38 (brain:blood ratio of 10) d. In addition, there was a dose-dependent difference in half-lives for some brain regions. These data clearly indicate that brain half-life is considerably longer than blood half-life in the monkey under conditions of chronic dosing.

Animals↗

Delayed neurotoxicity in monkeys exposed developmentally to methylmercury.

Five monkeys (Macaca fascicularis) were dosed from birth to 6.5-7.0 years of age with 50 micrograms/kg/day of mercury as methylmercuric chloride. Blood mercury levels were 0.6-0.9 ppm throughout most of the period of dosing. Blood mercury levels declined rapidly after cessation of dosing to levels below 0.01 ppm. When these monkeys were approximately 13 years old, some individuals displayed clumsiness during routine exercise. This observation was examined by cage-side observation and independent clinical neurological assessment by two staff veterinarians. Fine motor performance was assessed by timing retrieval of raisins from recessed grids. Treated monkeys took longer to retrieve raisins than age-matched controls. Clinical neurological assessment revealed apparent insensitivity to touch and pin-prick in mercury-exposed monkeys, and exposed monkeys were clumsier and slower in the exercise cage. These results indicate that overt signs of toxicity can be manifested long after exposure to methylmercury has ceased.

Animals↗

Quantification of operant behavior.

The study of performance on intermittent schedules of reinforcement has proved to be a powerful tool in the fields of experimental psychology and behavioral pharmacology and presently is proving equally valuable in behavioral toxicology. The ability to specify precisely contingencies of reinforcement allows a careful and detailed quantification of performance. Intermittent schedules of reinforcement may be used in behavioral toxicology in a number of ways. A baseline of performance may be established and utilized to monitor acute effects or to track effects of chronic exposure to a toxic agent. Alternatively, schedules of reinforcement may be used in experiments requiring group comparisons, where both terminal performance and acquisition of performance may be of interest. The use of different schedules, generating different rates and patterns of performance, may be compared to elucidate behavioral mechanisms. Use of computers for schedule control and data acquisition allows a detailed analysis of performance, thus increasing the probability of the detection of subtle effects.

Animals↗

Restoration of the foot using the radial forearm flap.

Large foot defects unsuitable for reconstruction by local foot flaps are most expediently salvaged with distant free-tissue transfers. Although muscle flaps are preferred for infected wounds, coverage of the clean or acute foot deformity may be better achieved with the innervated radial forearm fasciocutaneous flap. This almost ideal donor site has been used by us for all traumatic foot defects requiring free flaps during the previous year. Our results document that in the 5 available clinical examples, restoration of normal foot contour, durability during ambulation, and an excellent aesthetic appearance were achieved.

Adolescent↗

A new double-armed microsuture.

A new double-armed microsuture using 70-mu micro-edge taper-point (M.E.T., Sharpoint, Reading, PA) needles swaged onto 10-0 (22 mu) monofilament nylon has been developed by us primarily to allow precision intraluminal suture placement. Applications of this minimally atraumatic double-armed suture in microvascular surgery include patching and tacking within the anastomotic region.

Humans↗

Analysis of collagen content in the fetal wound.

The absence of apparent scar formation following the creation of surgical wounds in utero appears to be a phenomenon peculiarly privileged as a sequela of fetal wound healing. Little information exists to explain this disparity from our knowledge of adult wound healing. Therefore, following creation of surgical wounds in fetal rats, at different intervals the healing wounds were harvested and analyzed for collagen content and types. The average proportion of type III collagen was elevated in normal (26.5%) as well as wounded fetal skin (33.8%) when compared with normal levels for the adult (15%). The total collagen content was markedly diminished in the fetal wound. Although embryonal collagen synthesis apparently does exist in fetal reparative processes, the relationship to the lack of gross scarring remains undetermined.

Animals↗

Type I and type III collagen content of healing wounds in fetal and adult rats.

Full-thickness, dermal wounds were surgically created on the dorsa of fetal rats on the 17th day of gestation. The granulation tissue which developed after 2 days (19 days of gestation) was harvested from six to nine animals and pooled and the collagen was extracted with 0.5 M acetic acid and acetic acid plus pepsin. The ratio of type III:type I collagen was estimated from densitometer scans of electrophoretically separated alpha-chains. Full-thickness (to fascia depth) wounds were also produced on the dorsa of adult rats and granulation tissue which had developed for different periods of time up to 30 days was excised. Relative proportions of type III and type I collagen were assessed in normal and granulation tissues taken from the adult rats. Both fetal and adult granulation tissues have elevated type III collagen content but normal fetal tissue has a much higher content of type III than does normal adult tissue.

Animals↗

Adverse pregnancy outcome in the monkey (Macaca fascicularis) after chronic caffeine exposure.

Caffeine and the related methylxanthine theophylline are consumed regularly by pregnant women. In a study originally designed to assess the neurotoxic potential of caffeine in the infant, 40 female monkeys (Macaca fascicularis) were divided into three groups and administered caffeine in their drinking water at concentrations equivalent to 0, 10 to 15 or 25 to 35 mg/kg/day of caffeine 7 days a week. After a period of adaptation to caffeine these monkeys were mated with untreated males. Reproductive failure in the form of stillbirths and miscarriages was observed in the treated groups. Subsequently, 12 control monkeys and 1 low-dose monkey were added to the study and most of the original monkeys rebred. The second round of pregnancies confirmed that the treated monkeys had an increased rate of stillbirths and miscarriages. The precise cause of death of the stillborn infants could not be determined. Maternal weight gain and infant birth weights decreased in a dose-related manner. These results indicate that in utero exposure to methylxanthines (caffeine and/or its major metabolite theophylline) adversely affects pregnancy outcome in the monkey.

Abortion, Veterinary↗

Chronic low-level lead exposure in monkeys does not affect simple reaction time.

Simple visual reaction time was measured in a group of adult monkeys (Macaca fascicularis) dosed continuously with lead from birth onward, and in matched controls. Blood lead concentrations had been stable for 6 years at 33 micrograms/dl at the time of testing. The monkey was required to make contact with a stainless steel bar to initiate a trial, and release it at the onset of a visual cue. Delays between one and 13 sec were interposed between the initiation of the trial and the onset of the cue light in a semi-random manner over the course of each session. Reaction times did not differ between groups. Reinforcement was then made contingent upon progressively shorter reaction times until performance deteriorated to a specified level. Treated monkeys were able to respond as rapidly as controls. Simple reaction time proved insensitive to impairment by lead exposure, in contrast to other measures of performance tested in this group of monkeys.

Animals↗

Schedule-controlled behavior in infant and juvenile monkeys exposed to lead from birth.

Monkeys (Macaca fascicularis) were dosed orally from birth with 0 or 2000 micrograms/kg/day of lead as lead acetate. Blood lead concentrations of treated monkeys peaked at an average of 115 micrograms/dl by 100 days of age, and decreased to a steady state level of 33 micrograms/dl after withdrawal from infant formula at 270 days of age. No overt signs of toxicity were observed. Beginning at 60 days of age, monkeys were tested on a fixed ratio (FR) schedule of reinforcement, followed by a fixed interval (FI) schedule. Infants were tested in their home cages for 16 hours each day. When these monkeys reached three years of age, performance on a multiple fixed interval-fixed ratio schedule was evaluated. Infant performance was characterized by increased FR pause and decreased FI pause in the treated monkeys. Juvenile performance of lead-treated monkeys was characterized by increased Fl run rate, pause time, and index of curvature. Treated monkeys exhibited increased variability of performance both within and between sessions on several measures of Fl and FR performance.

Animals↗

Low-level lifetime lead exposure produces behavioral toxicity (spatial discrimination reversal) in adult monkeys.

Cynomolgus monkeys (Macaca fascicularis) were dosed from birth with 0, 50, or 100 micrograms/kg/day of lead. This regimen resulted in blood lead concentrations of 3, 15, or 25 micrograms/dl, respectively, before withdrawal of infant formula at 200 days of age. Blood lead concentration declined thereafter over the next 100 to 150 days to steady-state concentrations of 3, 11, or 13 micrograms/dl. At 9 to 10 years of age, these monkeys were tested on a series of spatial discrimination reversal problems. The monkey was required to respond on the right-most of two push buttons in order to receive a fruit-juice reward. When the task was learned, the left-most button became correct for a total of 15 such reversals on each of three tasks. The stimuli for the first task included no irrelevant cues, the second task included irrelevant form cues, and the third task included irrelevant form and color cues. Treated monkeys were impaired relative to controls in the presence but not in the absence of irrelevant cues. Moreover, the lower dose group was impaired only during the first task after the introduction of irrelevant stimuli, but not after irrelevant stimuli were familiar. These findings represent behavioral impairment in adult monkeys as a result of lifetime lead exposure resulting in blood lead concentrations that are typical for humans in industrialized environments.

Animals↗

Skin deepithelialization using the carbon dioxide laser.

Skin deepithelialization is an integral part of many reconstructive procedures, but it can be a tedious and time-consuming ordeal when using conventional techniques. The carbon dioxide laser has been used in rats to facilitate skin deepithelialization with no adverse effect on the expected wound healing. These findings have been extrapolated for clinical applications in allowing rapid creation of the dermal pedicle required for mammaplasty.

Animals↗

Primate research: relevance to human learning and development.

The monkey has proved an extremely useful model with which to examine the effects of developmental exposure to neurotoxic agents such as lead. Like humans, monkeys have a long period of gestation, infancy and sexual immaturity during which they continue to develop. This long period of vulnerability allows investigation of critical variables concerning sensitive periods of exposure. The nervous system of the monkey is very similar to humans and often responds to toxic insult like the human system. The behavioral repertoire of the monkey is also more like the human than is that of other laboratory species. Monkeys were exposed from birth with doses of lead that resulted in blood lead concentrations observed routinely in the population of children, and which are presently considered safe. Behavioral impairment was observed consistently in those monkeys on measures of activity, attention and memory, distractibility, adaptability and learning ability. Impairment persisted into adulthood.

Animals↗

Fatal pneumococcal meningitis in a colony-born monkey (Macaca fascicularis).

This report describes the clinical course and pathological findings in a four-year-old male cynomolgus monkey (Macaca fascicularis) which succumbed to fulminant pneumococcal meningitis. The extremely rapid course of this infection emphasizes the importance of early recognition of the clinical manifestations of meningitis in the correct diagnosis and rapid treatment of the condition.

Animals↗

Objective monitoring for safe tissue expansion.

The high incidence of complications during tissue expansion may be related to overexpansion with subsequent tissue necrosis and implant extrusion. Subjective parameters such as pain or capillary fill may be poor guidelines for determining the end point of a given session of expansion. In an attempt to rectify this problem, we have shown in a prospective study of eight consecutive patients that noninvasive objective monitoring utilizing transcutaneous measured oxygen levels, local perfusion, and implant pressures allowed us to quickly and safely expand each patient. Although perhaps cumbersome for routine use, this system proved valuable in complicated situations where subjective parameters could not be observed.

Adolescent↗