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Biomedical subjects

D Caldwell

Publications and source records attributed to D Caldwell.

At least 19 recordsLinked to original sources

Effect of the seaweed Ascophyllum nodosum on lambs during forced walking and transport.

The objective of this study was to determine the effect of feeding Ascophyllum nodosum (ANOD) to lambs at 0 (control), 0.5, 1, or 2% of DMI/d for 2 wk on lamb physiology in response to forced walking and transport during hot weather. Forty-four lambs (26 kg +/- 4.3) were used, and each lamb swallowed 3 gelatin capsules filled with ANOD or their normal 16% CP, pelleted grain ration twice daily, with the amount of ANOD dependent on the treatment. The amount of ANOD did not affect ear canal temperature or cortisol concentrations during 60 min of forced walking. The range between the minimum and maximum ear canal temperature for each lamb during 12 h of transport was narrower in lambs receiving the 2% ANOD than the control group (P = 0.05), and the 2% ANOD group also had lower (P = 0.05) ear canal temperatures than the control group during hot periods of transport. After 4 (P = 0.09) and 8 h (P = 0.05) of transport, the control group tended to have greater cortisol concentrations than the 2% ANOD group. Many differences among treatments were found in plasma protein, albumin, calcium, phosphorus, glucose, blood urea nitrogen, aspartate aminotransferase, magnesium, sodium, potassium, and chloride concentrations posttransport; mainly, the control and 0.5% ANOD groups had greater (P < 0.05) concentrations than the other 2 treatments. Aldosterone concentrations were greater in the control and 0.5% ANOD group than in the 1 and 2% ANOD groups before transport, whereas the concentrations were not different after transport, suggesting pretransport concentrations were lowered by supplementation. The 1 and 2% ANOD groups lost more BW than the control group as a result of transport (P = 0.04). After transport, no differences were observed in the latency for lambs to drink, eat, or lay. There was a suppression of the IgG and IgM antibody responses at 4 and 7 d after administration of ovalbumin, with greater ANOD supplementation rates suppressing antibody response the greatest. Although ANOD decreased ear canal temperature in hot periods of transport, stabilized electrolyte concentrations, and decreased cortisol throughout transport, it also suppressed the antibody response indicating that the effect of ANOD on immune function merits further investigation.

Animals↗

Phase II trial of intravenous lobradimil and carboplatin in childhood brain tumors: a report from the Children's Oncology Group.

BACKGROUND: [corrected] Lobradimil is a synthetic bradykinin analog that rapidly and transiently increases the permeability of the blood-brain barrier (BBB). The combination of lobradimil and carboplatin was studied in pediatric patients with primary brain tumors in a phase II trial, the primary endpoints of which were to estimate the response rate and time to disease progression. PATIENTS AND METHODS: Patients were stratified by histology into five cohorts: brainstem glioma, high-grade glioma, low-grade glioma, medullobastoma/primitive neuroectodermal tumor (PNET), and ependymoma. Patients received carboplatin adaptively dosed to achieve a target AUC of 3.5 mg min/ml per day (7 mg.min/ml/cycle) intravenously over 15 min on 2 consecutive days and lobradimil 600 ng/kg ideal body weight/day on 2 consecutive days each 28 day cycle. RESULTS: Forty-one patients, age 2-19 years, were enrolled; 38 patients, including 1 patient ultimately determined to have atypical neurocytoma, were evaluable for response. No objective responses were observed in the brainstem glioma (n=12) and high-grade glioma (n = 9) cohorts, although two patients with high-grade glioma had prolonged disease stabilization (>6 months). The study was closed for commercial reasons prior to achieving the accrual goals for the ependymoma (n = 8), medulloblastoma/PNET (n = 6) and low-grade glioma (n = 2) cohorts, although responses were observed in 1 patient with PNET and 2 patients with ependymoma. CONCLUSION: The combination of lobradimil and carboplatin was inactive in childhood high-grade gliomas and brainstem gliomas.

Adolescent↗

Oral (gavage), in utero and post-natal exposure of Sprague-Dawley rats to low doses of tributyltin chloride. Part II: effects on the immune system.

The immunotoxic effects of tributyltin chloride (TBTC) were examined in the offspring of Sprague-Dawley rats exposed in utero from day 8 of gestation, through lactation and post-weaning until pups reached the age of 30 days (male and female), 60 days (female) and 90 days (male). Daily oral (gavage) doses of 0.025, 0.25 and 2.5 mg/kg body weight/day were administered in olive oil 7 days/week. Immunologic endpoints were investigated at the termination of each study. Statistically significant results (P<0.05) included the following: At 30 days, the mean percent and absolute natural killer (NK) cell numbers were increased in male and female rats treated with the high TBTC dose. At 60 days, female rats had increased mean serum IgM levels at the low and high TBTC doses, increased mean percentage CD4(+)8(+) (immature) T lymphocytes at the middle and high doses, a non-linear dose-response increase in NK cell activity at the 50:1 and 100:1 effector:target cell ratios (pairwise comparisons significant at the low dose compared with control), and increased mean numbers of L. monocytogenes colony-forming bacteria on Day 2 post-infection (significant for trend) and Day 3 post infection (pairwise comparisons significant only in the middle dose). The 90-day male rats had decreased mean serum IgA levels at the middle dose group; increased IgM levels at the high dose group, increased IgG levels at the middle and high doses; decreased IgG2(a) in the high dose compared to the control; a dose-related increase in the mean percentage NK cell numbers (pairwise comparisons significant at the high dose compared with the control) and increased mean NK cell activity (pairwise comparisons significant at all dose groups compared with the control). The delayed-type hypersensitivity response to oxazolone was increased in the low and middle doses and decreased in the high dose. Thymus atrophy was observed in the high TBTC dose across all ages. Thus, in utero and post-natal treatment of F1 rats with low levels of TBTC affected some aspects of humoral and cell mediated immunity as well as the number and function of cells which are involved in the host's immunosurveillance mechanisms against tumours and viral infections.

Administration, Oral↗

Oral (gavage), in utero and postnatal exposure of Sprague-Dawley rats to low doses of tributyltin chloride. Part 1: Toxicology, histopathology and clinical chemistry.

Tributyltin (TBT) is a biocide that contaminates foods, especially shellfish. TBT is an endocrine disrupter in several marine species and is neurotoxic and immunotoxic in mammals. We have examined the effects of exposure to low doses of tributyltin chloride (TBTC) from day 8 of gestation until adulthood. Pregnant rats were gavaged daily with 0, 0.025, 0.25 or 2.5 mg TBTC/kg body weight from day 8 of gestation until weaning. Stomach contents of suckling pups contained undetectable levels of TBT and dibutyltin (DBT) levels were detectable only in the highest TBTC dose used, indicating negligible lactational transfer to pups. Post weaning, pups were gavaged daily with the same dose of TBTC administered to their mothers and sacrificed on post-natal days (PND) 30 (males and females), 60 (females) and 90 (males). TBTC had no effects on dams' body weights, food consumption, litter size, sex ratio or survival of pups to weaning. However, all doses of TBTC significantly affected parameters of the growth profile of the pups (mean body weights, average slope, curvature) and the ratio of weekly food consumption to weekly body weight gain indicated enhanced food conversion to body mass in females but a decreased conversion in males. Liver, spleen and thymus weights were also affected by TBTC. In male pups dosed at 2.5 mg/kg/day, reduced serum thyroxine levels were evident, indicating that the thyroid is a target for TBTC toxicity. No histopathological lesions were seen in the liver but elevated serum alanine aminotransferase, gamma-glutamyl transferase and amylase indicated hepatotoxicity. Significant decreases in liver weights in female pups exposed to 0.025 mg/kg/day TBTC were observed at PND 60. Decreases in spleen and thymus weights also pointed towards toxic effects of TBTC on the immune system. The 0.025 mg/kg/day TBTC should have been a no affect dose and yet this dose caused significant effects on growth profiles, decreased liver weights and elevated serum GGT levels in females.

Administration, Oral↗

A depletable pool of adenosine in area CA1 of the rat hippocampus.

Adenosine plays a major modulatory and neuroprotective role in the mammalian CNS. During cerebral metabolic stress, such as hypoxia or ischemia, the increase in extracellular adenosine inhibits excitatory synaptic transmission onto vulnerable neurons via presynaptic adenosine A(1) receptors, thereby reducing the activation of postsynaptic glutamate receptors. Using a combination of extracellular and whole-cell recordings in the CA1 region of hippocampal slices from 12- to 24-d-old rats, we have found that this protective depression of synaptic transmission weakens with repeated exposure to hypoxia, thereby allowing potentially damaging excitation to both persist for longer during oxygen deprivation and recover more rapidly on reoxygenation. This phenomenon is unlikely to involve A(1) receptor desensitization or impaired nucleoside transport. Instead, by using the selective A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine and a novel adenosine sensor, we demonstrate that adenosine production is reduced with repeated episodes of hypoxia. Furthermore, this adenosine depletion can be reversed at least partially either by the application of exogenous adenosine, but not by a stable A(1) agonist, N(6)-cyclopentyladenosine, or by endogenous means by prolonged (2 hr) recovery between hypoxic episodes. Given the vital neuroprotective role of adenosine, these findings suggest that depletion of adenosine may underlie the increased neuronal vulnerability to repetitive or secondary hypoxia/ischemia in cerebrovascular disease and head injury.

Adenosine↗

Abdominal wound with enterocutaneous fistula: a case study.

The care of an elderly male surgical patient with an enterocutaneous fistula located in an abdominal wound is described. The fistula is believed to have been related to multiple surgeries, wound dehiscence, and malnutrition. This article presents a brief overview of enterocutaneous fistulas and a pictorial demonstration of an alternative wound management technique that was used intermittently over several months to contain corrosive intestinal effluent until a commercial wound manager could be instituted.

Aged↗

Septo-optic dysplasia: the clinical insignificance of an absent septum pellucidum.

Neurodevelopmental assessments were performed on seven patients with optic nerve hypoplasia and absence of the septum pellucidum on MRI. The evaluation included neurological status, language development, neuropsychological functioning, and behavioral and emotional adjustment. Six of the seven were found to have normal cognitive development, intact neurological status, normal language development and age-appropriate behavior. Abnormal findings included early poor motor coordination, which was felt to be closely related to decreased visual acuity, as well as subtle visual attentional problems which occurred even in patients who had normal vision in one eye. Congenital absence of the septum pellucidum was not associated with significant intellectual, behavioral or neurological deficits in the majority of these patients.

Achievement↗

Continuing education requirements to maintain occupational therapy licensure.

Different states use a variety of regulatory mechanisms to monitor the quality of practice in occupational therapy. The requirement for mandatory continuing education has been adopted by fewer than half of American states, but there is reason to predict that this trend will increase. This study investigates the patterns linking licensure to continuing education and recommends actions to ensure uniformity and accountability.

Curriculum↗

A comparison of neuropsychological and psychosocial functioning after prophylactic treatment for childhood leukemia in monozygotic twins.

Outcome findings based on a comprehensive battery of neuropsychological and psychosocial measurements were compared for a set of monozygotic twins. One twin had been diagnosed with acute lymphoblastic leukemia and given prophylactic treatment involving intrathecal methotrexate. Her twin sibling, who developed no signs of the disease, served as a unique control. Remarkably similar profiles were noted for the twins on tests of nonverbal intelligence, visual memory, visual attention, psychomotor speed, and mental flexibility. All performances were in the average to high average range. Significant differences were found on tasks measuring verbal abstract reasoning skills. These differences were postulated to result from prophylactic treatment, leukemia itself, or disruption in normal psychosocial development. As in previous studies, problems with auditory attention were found. However, both children displayed attentional difficulties regardless of treatment status. Emotional assessment indicated that both twins were experiencing a clinically significant level of anxiety that was postulated to play a role in reduced attention skills. Findings argue for the continued need for monitoring the neuropsychological functioning of children given prophylactic treatment and demonstrate the importance of measuring emotional factors in assessment with these children.

Affective Symptoms↗

Early detection of carpal erosions in patients with rheumatoid arthritis: a pilot study of magnetic resonance imaging.

A pilot study comparing standard radiography to magnetic resonance imaging (MRI) was performed on the wrists of 10 patients with early (anatomic Stage I or II) rheumatoid arthritis (RA). MRI was found to be superior to standard radiographs in 2 respects: (1) synovial inflammation was impressively demonstrated on T2 weighted images, whereas plain films merely suggested soft tissue swelling; and (2) T1 and T2 weighted images clearly revealed erosions of several carpal bones which were not noted on standard radiographs. Although the expense of MRI currently precludes its routine use in clinical practice, the apparent sensitivity of this diagnostic modality for detecting early changes in RA might make it an invaluable tool for therapeutic decision making or for assessing response in interventional trials.

Adult↗