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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

Gender-based analysis of esophageal cancer patients undergoing preoperative chemoradiation: differences in presentation and therapy outcome.

The purpose of this study was to identify gender-dependent differences in presentation at baseline and therapy outcome in esophageal carcinoma patients treated with preoperative chemoradiotherapy (CTRT). We stratified patients according to gender and statistically compared pretreatment clinical stage, post-CTRT effect on carcinoma in the resected specimen, overall survival (OS), and patterns of failure. Of the 235 patients who underwent preoperative CTRT, 203 were men and 32 were women. Carcinomas in women correlated significantly with clinical stage II classification (78%vs. 55%) while cancers in men correlated significantly with clinical stage III classification (39%vs. 16%; P = 0.02). Carcinomas in women also correlated significantly with lower clinical N classification; more women had cN0 (52%) compared to men (28%; P = 0.01). Similarly, in the surgical specimens, more women had pN0 (78%) compared to men (64%; P = 0.06). At a median follow-up of 37 months, 10% more women than men remain alive (63%vs. 53%; P = 0.3). Distant metastases-free survival time was longer for women than men. Our results suggest that localized esophageal carcinoma is diagnosed in more advanced stages in men than in women. The reasons for these differences remain unclear and further expansion of these observations and study of biologic differences that might exist are warranted.

Chemotherapy, Adjuvant↗

Surgical management of duodenal leiomyomas.

Duodenal leiomyomas are rare neoplasms and when present are usually asymptomatic. There are, however, isolated case reports of such leiomyomas giving rise to complications including gastrointestinal hemorrhage and obstruction. The purpose of this study was to review the surgical experience with duodenal leiomyomas at a large tertiary referral center. A retrospective review was performed of all patients with histologically proven duodenal leiomyomas encountered from 1975 to 1995. Twelve patients with surgically treated duodenal leiomyomas were identified. There were eight men and four women with a mean age of 57 years (range 20-73 years) at diagnosis. Anemia was the presenting sign in 10 patients (83%). The mean hemoglobin level at presentation was 10.8 +/- 2.67 g/dl. Other presenting signs included melena (n = 5) and epigastric tenderness (n = 4). No patient had obstructive symptoms. Upper endoscopy visualized the lesion in 9 of 10 patients, but endoscopic biopsy provided an accurate histologic diagnosis in only two of six patients biopsied. All resected specimens underwent frozen section and permanent histopathologic analysis. Local excision was performed in eight patients, as benignancy was anticipated at surgical exploration and frozen section findings. Two patients underwent segmental duodenal resection with primary end-to-end anastomosis, and two patients underwent a Whipple procedure. There was no perioperative mortality. Morbidity was minimal. There was no tumor recurrence during a median follow-up of 8.4 years. Gastrointestinal blood loss is the most common complication of duodenal leiomyomas requiring surgical intervention. Small symptomatic leiomyomas with benign features may be safely treated with local excision.

Adult↗

Comparison of a new method for computer analysis with standard techniques for measuring survival rates in the rat transverse rectus abdominis musculocutaneous flap.

Many methods have been used to measure experimental flap survival in animal models. These have previously included planimetry, computer programs, and (routinely by the authors) the simple measurement of the weight of a template traced according to the dimensions of a given flap. To test the validity of their method, an alternative technique was developed by the authors' biostatiticians. Initially, in a study of rat transverse rectus abdominis musculocutaneous (TRAM) flaps, all templates were also scanned electronically to form bitmaps. Using commonly available software programs, each bitmap was colorized corresponding to viable and nonviable areas of the flaps. A summation of individual pixels by color could then be used to calculate the percentage of flap survival. A comparison of both methodologies in 64 rat TRAM flaps found that the survival rate was slightly greater overall when a computer analysis had been performed (3.1 +/- 1.7%), but this was not a significant difference (p = 0.479). Thus, the previous standard method was proven reliable, but just as precise calculations are now possible using the convenience of any personal computer.

Animals↗

Intraoperative topical tetracycline sclerotherapy following mastectomy: a prospective, randomized trial.

BACKGROUND AND OBJECTIVES: Postoperative wound seromas are a frequent and troublesome occurrence after mastectomy. Recent reports have suggested the efficacy of topical sclerosants at reducing their formation. METHODS: A prospective, randomized, double-blinded trial was performed to examine the effect of intraoperatively administered topical tetracycline on the occurrence of postoperative mastectomy seromas. Thirty-two women were randomized to the control arm (normal saline) and 30 women to the tetracycline arm. In the treatment group, 100 ml (2 g) of tetracycline solution was administered topically to the chest wall and skin flaps prior to skin closure. The control group received an equal volume of normal saline. Patients were monitored for the development of postoperative wound seroma. RESULTS: There were no significant differences between groups regarding total volume of closed suction drainage, numbers of patients leaving hospital with drains in place, or duration of catheter drainage. Seroma formation 2 weeks postoperatively was greater in the tetracycline group than the control group (53% vs. 22%, P = 0.01). There were no differences between groups regarding the degree of postoperative pain, wound infection, or seroma formation 1 month postoperatively. CONCLUSIONS: Topical tetracycline is not effective at preventing post-mastectomy wound seromas.

Administration, Topical↗

Parallels between attention deficit hyperactivity disorder and behavioral deficits produced by neurotoxic exposure in monkeys.

Attention deficit hyperactivity disorder (ADHD) is a disability that affects between 3 and 7% of children, with a significant number of individuals continuing to be affected into adolescence and adulthood. ADHD is characterized in part by an inability to organize complex sequences of behavior, to persist in the face of distracting stimuli, and to respond appropriately to the consequences of past behavior. There are some parallels between the features of ADHD and the behavior of monkeys exposed developmentally to lead or polychlorinated biphenyls (PCBs), as evidenced by research from our laboratory. Both lead and PCB exposure produce deficits on discrimination reversal and spatial delayed alternation performance; treated monkeys exhibit deficits in their ability to change an already established response strategy and inhibit inappropriate responses. Monkeys exposed developmentally to lead or PCBs also perform differently from control monkeys on a fixed interval schedule of reinforcement, which requires the temporal organization of behavior using only internal cues. Whereas the etiology of ADHD is multifactorial, the possibility that neurotoxic agents in the environment contribute to the incidence of ADHD warrants attention.

Animals↗

Workshop to identify critical windows of exposure for children's health: neurobehavioral work group summary.

This paper summarizes the deliberations of a work group charged with addressing specific questions relevant to risk estimation in developmental neurotoxicology. We focused on eight questions. a) Does it make sense to think about discrete windows of vulnerability in the development of the nervous system? If it does, which time periods are of greatest importance? b) Are there cascades of developmental disorders in the nervous system? For example, are there critical points that determine the course of development that can lead to differences in vulnerabilities at later times? c) Can information on critical windows suggest the most susceptible subgroups of children (i.e., age groups, socioeconomic status, geographic areas, race, etc.)? d) What are the gaps in existing data for the nervous system or end points of exposure to it? e) What are the best ways to examine exposure-response relationships and estimate exposures in vulnerable life stages? f) What other exposures that affect development at certain ages may interact with exposures of concern? g) How well do laboratory animal data predict human response? h) How can all of this information be used to improve risk assessment and public health (risk management)? In addressing these questions, we provide a brief overview of brain development from conception through adolescence and emphasize vulnerability to toxic insult throughout this period. Methodological issues focus on major variables that influence exposure or its detection through disruptions of behavior, neuroanatomy, or neurochemical end points. Supportive evidence from studies of major neurotoxicants is provided.

Adolescent↗

Identification of functional domains affected by developmental exposure to methylmercury: Faroe islands and related studies.

The Faroe Islands study is a prospective study designed to assess the neurological and behavioral consequences of in utero exposure to methylmercury (meHg). Maternal exposure to meHg was through consumption of fish and intermittent higher-level exposure through pilot whale meat, while consumption of pilot whale blubber resulted in maternal exposure to PCBs. Analysis of the neurobehavioral domains affected revealed impairment in attention, memory, and auditory processing, impairment in primary auditory function, and to a lesser extent motor impairment. For four of the eight endpoints affected by meHg exposure atp < .10, impairment was also correlated (p < .10) with in utero PCB exposure as measured by cord tissue PCB levels. Further analyses provide evidence for an independent effect of PCBs and meHg on these endpoints. Cross-sectional studies in a smaller number of children in the Amazon and Madeira by the same group of investigators, in which average meHg maternal hair levels were about twice as high those in the Faroe Islands, identified auditory, visual, and/or motor deficits, with little or no evidence of deficits in attention or memory. However, the results of the cross-sectional studies must be interpreted with caution, due to limited statistical power as well as a lack of opportunity to correlate effects to in utero exposure.

Animals↗

Behavioral impairment produced by low-level postnatal PCB exposure in monkeys.

The preponderance of evidence in humans suggests that polychlorinated biphenyl (PCB)-induced behavioral deficits result from prenatal exposure rather than exposure through breast milk, although a recent study reported lower psychomotor scores during infancy associated with PCB concentration in breast milk. In the current study, monkeys were dosed from birth to 20 weeks of age with a PCB congener mixture representative of the PCBs found in human breast milk. Blood and fat levels of PCB-exposed monkeys at the end of the dosing period were within the range observed in the general human population, while levels in control monkeys were below averages observed in humans in industrialized countries. Behavioral assessment on a series of tasks was performed when monkeys were between 2.5 and 5.0 years of age. Robust deficits were observed on spatial delayed alternation, fixed interval, and differential reinforcement of low rate performance. No group differences were observed for the number of errors on a series of nonspatial and spatial discrimination reversal tasks. Behavioral deficits included retarded learning, perseverative behavior, and inability to inhibit inappropriate responding. These results have implications for the potential contribution of exposure to PCBs through breast milk to behavioral impairment.

Animals↗

Induction of antitumor immunity after cure of pulmonary metastases, using staphylococcal enterotoxin B and bispecific antibody.

The combination of staphylococcal enterotoxin B (SEB) and anti-p97 x anti-CD3 bispecific antibody (bsAb) cures 60%-80% of mice with established pulmonary metastases of the syngeneic p97+ murine melanoma, CL62. We investigated the ability of cured mice to generate protective antitumor immunity. In tumor rechallenge experiments, CL62-cured mice developed protective immunity against rechallenge with CL62. The majority of mice also rejected the p97-negative parental cell line, K1735, indicating an immune response to tumor antigens common to both cell lines that were not bsAb-targeted. A significant humoral response developed against p97 antigen, but not against other antigens common to both CL62 and K1735. That the majority of cured mice nevertheless rejected K1735 suggests that tumor immunity is not antibody-dependent. Evidence of cellular immunity was obtained from the results of delayed-type hypersensitivity, proliferation and cytotoxicity assays, which revealed the presence of tumor-specific memory in bsAb-treated, CL62-cured mice. CD8+ T cells from cured, but not control mice were able to lyse tumor; however, memory CD4 cells had no cytolytic function. In vivo, however, both CD4 and CD8 T cells were required for effective protective immunity. These studies demonstrate that treatment with SEB and bsAb not only confers passive immune effects of tumor eradication, but also actively promotes the generation of a host antitumor immune response.

Animals↗

Consideration of the UltraPulse carbon dioxide laser as a tool for skin deepithelialization.

Laserbrasion is essentially skin deepithelialization. The continuous-wave carbon dioxide (CO2) laser has a long history during which this capability to ablate the epidermis has been used in multiple clinical applications. The "improved" UltraPulse CO2 laser has been advocated as a safer method, primarily for skin resurfacing. The authors show in Sprague-Dawley rats by gross and histological examination that the UltraPulse CO2 laser can also be used effectively to achieve skin deepithelialization, with efficacy in clinical simulations without untoward effects on wound healing. The advantage of the UltraPulse CO2 laser appears to be less destruction to surrounding tissues.

Animals↗

Comparison of visual function at adulthood and during aging in monkeys exposed to lead or methylmercury.

Of critical importance is the issue of whether exposure to a neurotoxic agent early in life or over a major portion of the lifespan can result in an age-related accelerated decline in neurological function. There is evidence in humans and animals that exposure to methylmercury may produce delayed neurotoxicity associated with aging. While lead is a ubiquitous pollutant, the potential of long-term lead exposure to accelerate age-related functional decline in nervous system function has apparently not been explored. In the current study, visual function assessed during adulthood was compared to results during aging in monkeys exposed to 500 or 2000 microg/kg/day of lead from birth onward, 50 microg/kg/day of methylmercury from birth to seven years, or 10, 25, or 50 microg/kg/day of methylmercury throughout gestation to four years of age. Spatial contrast sensitivity functions and visual fields were assessed in methylmercury-exposed monkeys, and spatial and temporal contrast sensitivity functions were assessed in monkeys exposed to lead. The frequency and amplitude at peak sensitivity and the high-frequency cut-off were compared at the two assessment periods for the contrast sensitivity functions. Age-related decrements were observed on both spatial and temporal visual function for all parameters. Treatment-related effects were observed in the monkeys exposed to methylmercury in utero and postnatally during the first assessment period but not during aging, whereas lead-exposed monkeys exhibited differences in temporal visual function at the first assessment but not the second. There was no evidence for accelerated decline in contrast sensitivity as a result of exposure to either toxicant. However, four of 10 methylmercury-treated monkeys exhibited slight constriction of visual fields at the second assessment that had not been present earlier. These results extend previous findings of evidence for delayed neurotoxicity in the somatosensory and auditory systems of these methylmercury-exposed groups.

Aging↗

Age-related increase in auditory impairment in monkeys exposed in utero plus postnatally to methylmercury.

Hearing impairment and deafness have been reported as a result of developmental and adult exposure to methylmercury; however, objective assessment of auditory function is generally lacking. This study extends previous research in our laboratory in which monkeys exposed to methylmercury from birth to adulthood exhibited high-frequency hearing impairment. Monkeys (Macaca fascicularis) were exposed throughout gestation and postnatally until 4 years of age to 0, 10, 25, or 50 micrograms/kg/day mercury as methylmercuric chloride. When they were 11 and 19 years of age, pure-tone detection thresholds for six frequencies between 0.125 and 31.5 kHz were determined by means of a psychophysical (behavioral) procedure. At 19 years of age, all five methylmercury-exposed monkeys exhibited elevated pure-tone thresholds compared with controls. Impairment was generally observed across the full range of frequencies. Comparisons of performance at 11 and 19 years revealed relatively greater deterioration in function in treated compared with control monkeys. These results extend previously reported evidence of deficits in auditory function produced by postnatal methylmercury exposure, and describe a pattern of deficit across frequencies different than that observed in the previous study. This study also provides evidence for development or acceleration of impairment of auditory function during aging as a consequence of developmental methylmercury exposure.

Age Factors↗

Gains and losses of the XII-VII component of the "baby-sitter" procedure: a morphometric analysis.

The classic hypoglossal transfer to the facial nerve is invariably followed by complications caused by tongue atrophy. In 1984, Terzis introduced the "baby-sitter" procedure which involved a formal cross-facial procedure, in addition to partial neurectomy of the hypoglossal nerve, and an end-to-side coaptation with the ipsilateral facial nerve. This reported study provides, for the first time, quantification of the number of hypoglossal motor fibers needed to successfully restore eye sphincter function, using an end-to-side coaptation with preservation of the tongue. Thirty adult Sprague-Dawley rats were divided into six groups: control, denervated, perineurial window, 20 percent partial neurectomy (PN), 40 percent PN, and 80 percent PN. The procedure involves interposing a nerve graft (saphenous) between the partially severed XII nerve and the upper zygomatic branch of the facial nerve. Evaluation of the behavioral data (blink reflex) revealed good-to-superb return of the blinking mechanism in the 40 percent group, without significant tongue atrophy. Electrophysiologic data in the 40 percent neurectomy group demonstrated superiority to the other groups. Quantitative axonal morphometry of the coaptation sites and graft, as well as motor end-plates of the orbicularis oculi muscle and tongue showed the 40 percent partial neurectomy group to be the optimal group.

Animals↗

An endoscopic subcutaneous dissector for obtaining vein grafts.

Recent improvements in internal mechanical retractors have resulted in a commercially available endoscopic subcutaneous dissector that has an inverted pistol grip for ease of retraction, an end-mounted endoscope channel, and a distal, translucent spoon-shaped shield that maintains the optical cavity. This provides an effective reach that is valuable for the minimally invasive harvest of any long, narrow structure--the greater saphenous vein in particular--as shown in this preliminary study with 2 patients. Such extracted vein grafts taken grossly from above and below the knee appear normal. Long-term histological changes and rates of conduit patency are still unknown. The limited-access incisions necessary for this endoscopic vein harvest definitely are smaller, and can be oriented transversely to minimize further the disfigurement from any resulting scar when compared with traditional methods.

Endoscopes↗

Fate of the TRAM flap after abdominoplasty in a rat model.

During a classical abdominoplasty, all musculocutaneous perforators from the deep inferior epigastric vessels are normally divided. Even if somehow neovascularization could relink the abdominal skin and rectus abdominis muscles, reestablishing these same discrete perforators would be unlikely because of the barrier effect of the abdominal wall fascia. Therefore, a lower transverse rectus abdominis musculocutaneous (TRAM) flap intuitively should not regain sufficient vascularity for viability after a prior abdominoplasty, and a history of the latter should be expected to be a major contraindication for this procedure. Nevertheless, anecdotal observations of successful lower TRAM flaps following abdominoplasty seem to contradict our basic principles, which may need better further elucidation. Consequently, this two-stage study in Sprague-Dawley rats was undertaken, initially performing an abdominoplasty in all rats. This was followed 1 or 10 months later by the creation of an unipedicled superiorly based TRAM flap that incorporated virtually all of the abdominal skin. From our identical historical TRAM flap control (n = 5) except without prior abdominoplasty, 72.8 +/- 12.83 percent of this area survived. TRAM flaps raised 1 month after the abdominoplasty (n = 6) had 2.2 +/- 3.4 percent or essentially no viability. Unexpectedly, the long-term group (n = 7) demonstrated 13.7 +/- 10.0 percent viability, ranging from 0 to 30 percent. Both groups of TRAM flaps after abdominoplasty had a flap survival area significantly less than that of the control by two-tailed group t test (p < 0.001), and that of the long-term group area was significantly greater than that of the short-term (p = 0.022). Lead oxide studies 10 months after abdominoplasty revealed no irrefutable evidence of the reestablishment of rectus abdominis perforators to the integument, although obviously some reconnections had formed at the microcirculatory level to partially revascularize some flaps. The range of viability of the long-term rat TRAM flaps documented that for the majority, surviving surface area was minuscule even following a delay equivalent to a human decade after abdominoplasty (1 rat month - 1.1 human years), yet rarely sufficient revascularization did indeed occur, which could explain the prior unusual clinical successes. However, the basic principle that a TRAM flap raised following a classical abdominoplasty at any time would be a risky maneuver seems to still be a valid concept.

Abdominal Muscles↗

Effects of lifetime lead exposure on spatial and temporal visual function in monkeys.

Detailed characterization of several aspects of visual function was performed in two groups of monkeys (Macaca fascicularis) exposed to lead continuously from birth. One group of four monkeys was dosed from birth onward with 500 microg/kg/day of lead as lead acetate, while another group of six monkeys was dosed with 2000 microg/kg/day. Blood lead levels peaked in the former group at 50 microg/dl early in life; the latter group had peak blood lead concentrations averaging 115 microg/dl during infancy. Blood lead concentrations decreased before one year of age to stable levels of 25 or 35 microg/dl in the low and high dose groups respectively. Spatial and temporal visual function was assessed using a psychophysical procedure at 7-9 years of age. Six age-matched controls were tested concurrently. Two treated monkeys had severe hyperopia: one was assessed on temporal vision only and the other was not assessed. Spatial data from a third monkey were considered suspect and excluded. Six of the nine treated monkeys in which temporal vision was assessed had thresholds below control values at low and/or middle frequencies under high luminance conditions. Low-luminance temporal vision was not affected. There was no evidence of impairment of spatial visual function in lead-exposed monkeys with normal refractive status at either high or low luminance. This study suggests that temporal visual function may be preferentially impaired as a result of lifetime exposure to a moderate body burden of lead, although these results require replication before definitive conclusions may be drawn.

Animals↗

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↗