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Biomedical subjects

D C Rice

Publications and source records attributed to D C Rice.

At least 19 recordsLinked to original sources

Effects of lifetime lead exposure in monkeys on detection of pure tones.

Increased detection thresholds for pure tones were observed in a large cohort of children exposed to lead environmentally while smaller studies in lead-exposed workers have reported conflicting results on assessments of auditory function. Pure tone detection thresholds were determined in a group of monkeys (Macaca fascicularis) dosed with 2 mg/kg/day of lead from birth through testing at 13 years of age. Blood lead concentrations were stable at about 30 micrograms/dl until monkeys were 10-11 years of age at which time they increased to between 50 and 70 micrograms/dl. Five age- and rearing-matched monkeys served as controls. Detection thresholds were determined at six frequencies between 0.125 and 31.5 kHz. Ear phones were fit over both ears, and thresholds were determined for each ear separately. The monkey signaled detection of the tone by breaking contact with a stainless steel bar. Three lead-exposed monkeys exhibited normal pure tone detection functions. Three monkeys had thresholds outside of the control range at some frequencies; there was a tendency for higher frequencies to be differentially more affected. These findings are consistent with reports of elevated pure tone thresholds in humans exposed to lead developmentally, although the effect is smaller than might have been predicted given the concurrent blood lead concentrations of these monkeys.

Acoustic Stimulation

Effect of long-term lead exposure on hematology, blood biochemistry, and growth curves in monkeys.

A total of 90 monkeys (Macaca fascicularis), comprising four study cohorts born over a seven-year period, were hand reared and dosed orally with lead or vehicle according to one of several protocols, in most cases from birth to 9-14 years. Blood lead concentrations of lead-exposed groups ranged from 10 to 90 micrograms/dl depending on dose and age. Routine hematology and blood biochemistry analyses were performed regularly. Comparison of treated groups at various ages to the appropriate control group revealed no strong indication of lead-related effects. In addition, body weight increase was modeled from days 30-3500 of age in subset of this larger group, including 52 monkeys exposed to vehicle or lead during development according to one of four regimens: vehicle, lead from birth onward, lead to 400 days of age, or lead beginning at 300 days of age. No effect of lead on body weight was found. These results suggest that lead exposure beginning early in life and continuing for as long as 14 years resulted in no overt toxicity, as measured by these parameters.

Aging

Effects of postnatal exposure to a PCB mixture in monkeys on nonspatial discrimination reversal and delayed alternation performance.

Behavioral impairment as a consequence of PCB exposure beginning in utero has been reported in both humans and animals. The present study assessed the behavioral consequences of postnatal exposure to PCBs. Male monkeys (Macaca fascicularis) were dosed from birth to 20 weeks of age with 7.5 micrograms/kg/day of a PCB mixture representative of the PCBs typically found in human breast milk (8 monkeys) or vehicle (5 monkeys). At 20 weeks of age, PCB levels in fat and blood of treated monkeys were 1.7-3.6 ppm and 2-3 ppb respectively. Beginning at three years of age, monkeys were tested on a series of nonspatial discrimination reversal problems followed by a spatial delayed alternation task. Treated monkeys exhibited decreased median response latencies and variable increases in mean response latencies across the three tasks of the nonspatial discrimination reversal. There were no group differences on accuracy of performance, although some treated individuals made more mistakes at the beginning of the experiment than did control monkeys. On the delayed alteration task, the PCB-exposed group displayed retarded acquisition of the task and increased errors at short delay values, which were tested at the beginning of the experiment. There was no increase in the total number of errors in treated monkeys at long delay values. Treated monkeys engaged in more perseverative responding than controls over the entire course of the experiment, in some instances even in the absence of an increase in overall error rate. These findings are interpreted as a learning/performance decrement rather than an effect on spatial memory per se. The results of this study suggest that PCB exposure which is limited to the early postnatal period and results in environmentally-relevant body burdens produces long-term behavioral impairment.

Adipose Tissue

Use of a micropunch for arteriotomy in end-to-side anastomosis.

A micropunch can mechanically create a precise, clean microarteriotomy that is a simple and perhaps more accurate method, especially in atherosclerotic vessels where plaque or the risk of intimal dissection may sometimes interfere with conventional incision or excision techniques. A 1.5-mm. prototype micropunch was tested in seven Sprague-Dawley rats to create;l an end-to-side femoral vein to artery fistula, with a traditional traction suture method used on the contralateral side as a control. All anastomoses were patent immediately and at 2 weeks, implying no compromise, even in small vessels, by using a micropunch. However, the technique had to be modified, as the 1.5-mm anvil could not be inserted directly into the vessel lumen because of the small size of the rat femoral artery. This indicates a significant limitation of this device for use in vessels with an internal diameter less than that of the chosen anvil size.

Anastomosis, Surgical

Lessons for neurotoxicology from selected model compounds: SGOMSEC joint report.

The ability to identify potential neurotoxicants depends upon the characteristics of our test instruments. The neurotoxic properties of lead, methylmercury, polychlorinated biphenyls, and organic solvents would all have been detected at some dose level by tests in current use, provided that the doses were high enough and administered at an appropriate time such as during gestation. The adequacy of animal studies, particularly rodent studies, to predict intake levels at which human health can be protected is disappointing, however. It is unlikely that the use of advanced behavioral methodology would alleviate the apparent lack of sensitivity of the rodent model for many agents.

Animals

Behavioral effects of lead: commonalities between experimental and epidemiologic data.

Enormous effort has been focused over the last decade and a half on characterizing the behavioral effects of lead in the developing organism. While age-appropriate standardized measures of intelligence (IQ) have been the dependent variable most often used to assess lead-induced cognitive impairment in epidemiologic studies, researchers have also used a variety of other methods designed to assess specific behavioral processes sensitive to lead. Increased reaction time and poorer performance on vigilance tasks associated with increased lead body burden suggest increased distractibility and short attention span. Assessment of behavior on teachers' rating scales identified increased distractibility, impulsivity, nonpersistence, inability to follow sequences of directions, and inappropriate approach to problems as hallmarks of lead exposure. Robust deficits in learned skills such as reading, spelling, math, and word recognition have also been found. Spatial organizational perception and abilities seem particularly sensitive to lead-induced impairment. Assessment of complex tasks of learning and memory in both rats and monkeys has revealed overall deficits in function over a variety of behavioral tasks. Exploration of behavioral mechanisms responsible for these deficits identified increased distractibility perseveration, inability to inhibit inappropriate responding, and inability to change response strategy as underlying deficits. Thus, there is remarkable congruence between the epidemiologic and experimental literatures with regard to the behavioral processes identified as underlying the deficits inflicted by developmental lead exposure. However, careful behavioral analysis was required from researchers in both fields for such understanding to emerge.

Animals

Sensory and cognitive effects of developmental methylmercury exposure in monkeys, and a comparison to effects in rodents.

Developmental exposure to methylmercury in the macaque monkey produced impairment of function in the visual, auditory, and somatosensory systems. In addition, delayed neurotoxicity was observed in monkeys years after cessation of dosing, manifested as overall clumsiness and slowness in reaching for objects. The effects of developmental methylmercury exposure on cognitive function in monkeys are more equivocal; both positive and negative results have been obtained, with no obvious pattern with regard to possible domains of impairment. Prenatal methylmercury exposure in rodents produced retarded development and impairment of motor function, while the evidence for cognitive impairment is less consistent. Derivation of reference doses based on the available data from monkeys and rodents is remarkably congruent, and is virtually identical to values derived from evidence for developmental impairment in humans. Research needs include determination of neurotoxic effects at lower body burdens in the monkey, including dose-effect data, and a more systematic exploration of the pattern of behavioral deficits in both primates and rodents.

Animals

Assessment of mercury neurotoxicity through psychometric and neurobehavioral testing: session summary.

Neurobehavioral disorders are well-recognized among the adverse health effects of exposure to mercury. The effort to characterize these effects in animals and humans has progressed steadily over several decades. This has included a variety of study designs, and employed a variety of measurement techniques to evaluate exposure of individuals and populations. The Twelfth International Neurotoxicology Conference, Neurotoxicity of Mercury: Indicators and Effects of Low-Level Exposure, included a plenary session on the predictive value of psychometric and neurobehavioral testing of animals and humans in assessing neurotoxic effects. This session provided a broad view of the methods currently in use to measure adverse effects on the nervous system, in particular those effects that might be attributed to mercury exposure.

Central Nervous System Diseases

Effects of developmental methylmercury exposure or lifetime lead exposure on vibration sensitivity function in monkeys.

Paresthesias are a frequently reported symptom of methylmercury exposure in adults, while peripheral neuropathy has long been known to result from high-level lead exposure. Despite this, no objective determination of somatosensory function has been performed in either humans or animals for either toxicant. Somatosensory function was assessed following developmental methylmercury exposure or lifetime lead exposure in monkeys (Macaca fascicularis) by determination of sensitivity to vibration applied to the fingertip. Vibration thresholds were determined over a number of frequencies, from 25 to 250 Hz, by means of a behavioral procedure. The underside of the tip of the monkey's middle finger was precisely positioned over a blunt probe attached to a vibrator. The monkey signaled detection of the vibration by breaking contact with a stainless steel bar with the free hand. At each of the five frequencies tested, the amplitude of the vibration was manipulated systematically to determine the monkey's threshold of detection. Four of five monkeys dosed with methylmercury from birth to 7 years of age, with blood mercury levels during dosing of 0.8-1.1 micrograms/g, exhibited elevated thresholds when tested at 18 years of age. Two monkeys dosed in utero through 4 years of age, with blood mercury levels of 0.35 micrograms/g during dosing, were impaired when tested at 15 years of age, while two monkeys with histories of blood mercury levels of 0.70 were relatively unimpaired. Lifetime exposure to lead resulting in stable blood lead levels of 20-25 micrograms/dl resulted in elevated vibration sensitivity only at the highest frequency in all four individuals tested. However, only two of six individuals with high lead levels (60-130 micrograms/dl) exhibited impairment. These results represent severe impairment in methylmercury-exposed monkeys 11 years after cessation of dosing and extend previous research documenting visual and auditory impairment in these monkeys. While effects of lifetime lead exposure on vibration sensitivity observed in the present study are suggestive, there is clearly a need for further research.

Animals

Silicone thorax: a complication of tube thoracostomy in the presence of mammary implants.

Rupture of silicone breast implants is usually either iatrogenic or due to trauma. We present a case of blunt chest wall trauma in a patient with bilateral breast implants. Emergency chest tube thoracostomy resulted in rupture of one of the prostheses and caused subsequent migration of silicone into the chest cavity, where it led to empyema. The patient ultimately required a thoracotomy to evacuate the silicone and decorticate the lung. Review of the literature and methods to avoid this complication are described.

Breast Implants

Physiologic superiority of the anatomic dominant pedicle of the TRAM flap in a rat model.

Despite an extensive knowledge of the anatomic nuances of the rectus abdominis muscle and corresponding relationship to the vascularization of the skin of the abdomen, the clinical outcome when used as a musculocutaneous flap cannot always be predictable. Only a few human physiologic studies have been attempted to explain this discrepancy. Further laboratory investigations of the anatomy and physiology of the rat transverse rectus abdominis musculocutaneous (TRAM) flap suggest that this is a safer, comparable, yet inexpensive animal model for studying further the dynamics of this flap. By caliber and course, the major source vessel to the rectus abdominis muscle in the Sprague-Dawley rat enters superiorly as the cranial epigastric artery, which is a continuation of the internal thoracic (mammary) artery. Anatomic dissections in 13 rats revealed, on average, that 4.7 +/- 0.97 large musculocutaneous perforators emanated from each cranial epigastric artery at regular intervals which then proceeded directly to the overlying abdominal integument. Just below the umbilicus, a watershed is formed by small "choke" anastomoses to a frequently vestigial caudal epigastric artery or, more commonly, a true anastomosis with a branch of the deep circumflex iliac artery. In 10 additional rats, TRAM flaps encompassing the skin of the entire abdominal wall were then elevated so as to rely on a single pedicle, alternating randomly from either source. By laser Doppler flowmetry, blood flow by means of the larger-caliber superior pedicle exceeded twice that of the subservient inferior pedicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Evidence for the efficacy of TRAM flap delay in a rat model.

The dilemma in selecting a variant of the transverse rectus abdominis musculocutaneous (TRAM) flap for autogenous tissue breast reconstruction is to balance maximal flap perfusion against the sacrifice of abdominal-wall integrity. A surgical delay has been suggested as one very simple fascia-sparing technique that simultaneously augments flap volume, but no randomized clinical studies have been performed to prove whether there is any benefit whatsoever following such a maneuver. Because large groups of nearly identical subjects may be more readily available for comparison in an animal model, the rat TRAM flap provides an inexpensive method to further investigate the delay phenomenon in this setting. Staged procedures were performed in 15 Sprague-Dawley rats initially causing a delay by division of one or both dominant vessels (cranial epigastric) supplying the rectus abdominis muscles. Either 2 or 4 weeks later, TRAM flaps were elevated based only on the subservient (caudal epigastric) pedicle. A control group of 7 rats with immediate formation of a TRAM flap had a mean survival of 46.3 +/- 15.37 percent of their original flap surface area. After a 2-week delay, viability was 50.2 +/- 17.54 percent for ipsilateral and 39.4 +/- 7.57 percent for flaps with prior bilateral dominant pedicle division. Neither was significantly different from control (p = 0.68 and 0.38, respectively). However, the ipsilateral 4-week delayed group had 67.8 +/- 8.96 percent flap survival, which represented a significant enhancement when compared with the undelayed control TRAM flaps (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles

Neurotoxicity of lead, methylmercury, and PCBs in relation to the Great Lakes.

There is ample evidence identifying lead, methylmercury, and polychlorinated biphenyls (PCBs) as neurotoxic agents. A large body of data on the neurotoxicity of lead, based on both epidemiologic studies in children and animal models of developmental exposure, reveals that body burdens of lead typical of people in industrialized environments produce behavioral impairment. Methylmercury was identified as a neurotoxicant in both adults and the developing organism based on episodes of human poisoning: these effects have been replicated and extended in animals. High-dose PCB exposure was recognized as a developmental toxicant as a result of several episodes of contamination of cooking oil. The threshold for PCB neurotoxicity in humans is less clear, although research in animals suggests that relatively low-level exposure produces behavioral impairment and other toxic effects. Tissue levels in fish below which human health would not be adversely affected were estimated for methylmercury and PCBs based on calculated reference doses (RfDs) and estimated fish intake. Present levels in fish tissue in the Great Lakes exceed these levels for both neurotoxicants. Great Lakes fish and water do not pose a particular hazard for increased lead intake. However, the fact that the present human body burden is in a range at which functional deficits are probable suggests that efforts should be made to eliminate point sources of lead contamination in the Great Lakes basin.

Adult

In utero caffeine exposure affects feeding pattern and variable ratio performance in infant monkeys.

Adult female monkeys (Macaca fascicularis) were exposed via their drinking water to 0.0, 0.15, or 0.35 mg/ml of caffeine prior to and throughout pregnancy. Caffeine exposure resulted in a dose-related increase in the number of infant deaths at parturition. Additional females were added to the control group and the original groups were rebred, which resulted in 16, 13, and 9 live infants in control, low-dose, and high-dose groups, respectively. During pregnancy the mean serum caffeine levels were 3.4 and 10.3 micrograms/ml and the mean serum theophylline levels were 6.6 and 12.9 micrograms/ml for the low-dose and high-dose groups, respectively. Infants were separated from their mothers at birth and reared in a primate nursery to facilitate evaluation of infant performance on a variety of behavioral tasks. Infant formula consumption was monitored by a computer-based system 19 hr per day until 30 days of age. At 30 days of age infants were trained to press a button for a formula reward, after which they performed on a variable ratio schedule for a 14-day period. Monitoring of feeding pattern revealed that the treated infants spent significantly more time feeding than controls. On the variable ratio schedule, the high-dose group had consistently longer pause times and longer interresponse times than the control group. The results from this study indicate that in utero exposure to caffeine and its metabolites results in altered behavioral patterns in infant monkeys.

Animals

Introduction to principles and procedures in behavioral testing.

This article serves as an introduction to the following two articles which describe the effects of drugs that interact with N-methyl-D-aspartate (NMDA) receptors on a number of behavioral baselines. The discussion in the subsequent articles focuses on detailed examination of performance on complex learning tasks, although effects of drugs affecting NMDA receptors on simple learned and unlearned behaviors are also mentioned. This article will provide a framework for interpretation of the results reported. To that end, a short primer on the principles of behavior is provided, followed by a description of a number of behavioral tests and discussion of issues important for the interpretation of results from such tests. The behavioral baselines discussed are, for the most part, the specific tasks from which data are presented in the following reports. A few additional descriptions have been included to illustrate specific points regarding data interpretation. The examples discussed are not necessarily representative of behavioral endpoints used routinely in the assessment of the behavioral effects of drugs. A number of reviews are available to the interested reader (Cabe & Eckerman 1982; Heise 1984; Rice 1990; Thompson & Shuster 1968; World Health Organization 1986).

Animals

Chylous fistula: an unusual occurrence after mastectomy with immediate breast reconstruction.

Postoperative lymphatic complications of mastectomy and immediate reconstruction are well documented, consisting predominantly of lymphorrhea, lymphocele, and chronic lymphoedema. Chylous fistula is a hitherto undescribed entity complicating breast surgery. It was managed successfully by cessation of oral intake and the use of intravenous fluids, as is recommended in the treatment of chylous fistulas occurring elsewhere in the body. Although these are exceedingly rare, all plastic surgeons doing breast reconstruction should be aware of chylous fistulas and their treatment.

Breast Neoplasms

Effects of in utero methylmercury exposure on a spatial delayed alternation task in monkeys.

Adult female monkeys (Macaca fascicularis) were exposed to 0, 50, 70, or 90 micrograms/kg/day of methylmercury prior to and throughout pregnancy and produced 11, 9, 2, and 2 infants, respectively. At birth, blood mercury levels of treated infants ranged from 1.04 to 2.46 ppm. At approximately 7 to 9 years of age, the monkeys were trained by successive approximation to respond on a lit button for a small amount of apple juice. The monkeys were then trained on a 0.1-sec spatial delayed alternation task to a specified criterion of performance. This was followed by 10 sessions each of fixed delay times of 0.5, 1, 3, 5, and 10 sec, followed by 20 sessions containing variable delay times of 0.1 to 15 sec. Data from all treated monkeys were combined. There were no differences between treated and control monkeys in initial button training or number of sessions to reach criterion on 0.1-sec delay procedure. On the fixed delay sessions, the treated monkeys had significantly more correct trials, and fewer incorrect responses, perseverative responses, and delay responses than controls. There were no differences between the treated and control monkeys on performance on the variable delay schedule. Results from this study indicate that in utero methylmercury exposure did not adversely affect the spatial memory of adult monkeys when tested on a delayed alternation task and may have facilitated performance on this task.

Animals

Effect of cystoscopy, prostate biopsy, and transurethral resection of prostate on serum prostate-specific antigen concentration.

To assess the effect of cystoscopy, prostate biopsy, and transurethral resection of the prostate (TURP) on the serum prostate-specific antigen (PSA) concentration, 101 patients were evaluated. For cystoscopic examination, 69 men were randomized in a prospective manner to one of three groups: flexible cystoscopy, rigid cystoscopy, and a control cohort. The median change in serum PSA was 0.1 ng/mL following flexible cystoscopy, 0.05 ng/mL after rigid cystoscopy, and 0.05 ng/mL for the control group, in which two serum PSA determinations were obtained without an intervening cystoscopy. The differences between the three groups were not statistically significant. The effect of prostate biopsy and TURP was examined in 32 men. Prostate biopsy caused an immediate elevation in the serum PSA level, with a median increase of 7.9 ng/mL (p < 0.0001). Similarly, TURP produced an elevation in the serum PSA concentration, with a median change of 5.9 ng/mL (p < 0.001). The median time required for the serum PSA value to return to a stable level after prostate biopsy was fifteen days (range: 5-21 days) for men with prostate cancer and seventeen days (range: 3-30+ days) for men without cancer, and eighteen days (range: 12-30+ days) for men who underwent TURP. These findings indicate that a serum PSA determination after either a flexible or a rigid cystoscopy is accurate and reliable. Both biopsy and TURP cause an immediate increase in the serum PSA level, which usually returns to a stable, baseline level within three weeks. However, because in some patients the serum PSA still remained elevated after four weeks, it is recommended that a serum PSA determination not be obtained for at least six weeks after either a prostate biopsy or TURP.

Aged