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Biomedical subjects

D A Wilson

Publications and source records attributed to D A Wilson.

At least 19 recordsLinked to original sources

The role of olfactory bulb norepinephrine in early olfactory learning.

Wistar rat pups were implanted with bilateral olfactory bulb cannulas on postnatal day 5 (PN5). On PN6, pups were trained in an olfactory classical conditioning task with peppermint odor as the CS and tactile stimulation/stroking as the UCS. Pups were randomly assigned to either PAIRED, BACKWARD or ODOR-only conditions. Half the pups in each group received intrabulbar infusions of 100 microM propranolol and half received intrabulbar infusions of saline during the training session. Propranolol infusions blocked acquisition of the learned odor preference expressed by PAIRED saline-infused pups. Diffusion of the infusate was checked in additional pups by infusing [3H]NE and performing LSC analysis. Infusate concentration did not significantly differ between the anterior and posterior halves of the bulb, but were sharply lower in the olfactory peduncle and more posterior areas. The results suggest that olfactory bulb NE is critical for early olfactory learning.

Animals

Elevated levels of acute phase plasma proteins in major depression.

Levels of acute phase and other plasma proteins were measured in 21 men with major depression, 28 men with alcohol dependence, and 12 men who acted as controls. The depressed men had significantly elevated levels of the acute phase proteins, haptoglobin and alpha-1-antichymotrypsin, and of immunoglobulin G. The elevations in haptoglobin and alpha-1-antichymotrypsin were highly correlated with each other, and were correlated with the severity of depression and negatively correlated with the thyroid stimulating hormone response to thyrotropin. The alcoholic men had elevated haptoglobin levels, but significantly decreased levels of immunoglobulin G. These findings provide further evidence for an inflammatory response during depression.

Acute-Phase Proteins

Blockade of mitral/tufted cell habituation to odors by association with reward: a preliminary note.

Association of odor and reward during the early postnatal period modifies rat pup behavioral responses and olfactory bulb neural responses to subsequent presentations of that odor. Recent evidence has shown that olfactory bulb output neurons, mitral/tufted cells, receive convergent odor and reward inputs. The present report demonstrates that contiguous odor-reward pairings prevent mitral/tufted cell habituation to the odor that normally occurs to repeated odor-only stimulation. It is hypothesized that the maintenance of olfactory bulb responses to conditioned odors during training may allow for activation of long-term memory mechanisms.

Animals

Effects of exercise test results on physician perceptions of coronary artery disease probability using a threshold analysis.

The incremental diagnostic value of exercise electrocardiographic testing compared with clinical data alone in the diagnosis of coronary artery disease (CAD) was found to be of limited value in a previous study. That study used a computer algorithm for diagnosing disease. Thus, the strict use of the results apply only to computerized disease diagnosis rather than physicians' diagnoses. The aim of the present study was to determine whether exercise test data improve a physician's ability to detect the presence or absence of CAD and 3-vessel or left main CAD, and whether the data effect the decision to perform angiography. The study sample comprised a data base of 312 patients whose clinical data, exercise test results and coronary anatomy were known. Individual cases were presented to 8 cardiologists with and without exercise data. The cardiologists provided estimates of disease probability and were asked whether they would request coronary angiography. Receiver-operating characteristic curves and goodness-of-fit analysis showed better discrimination and calibration of the estimates for the presence of CAD and 3-vessel/left main CAD after exercise test results were known. Individualized probability thresholds for deciding whether to request angiography were determined for each physician. Forty-three percent of patients crossed greater than or equal to 1 threshold, with 64% of the crossings in the correct direction. For estimating the presence of any CAD, 84% of crossings from below to above a threshold were correct, whereas only 36% from above to below were correct. For 3-vessel/left main CAD, 36% of crossings from below to above a threshold were correct, whereas 88% from above to below were correct.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Angiography

Diurnal profiles of thyroid hormones are altered in depression.

Free thyroxine index (FT4I), serum thyroxine (T4) and thyrotrophin concentrations were measured in 45 depressed subjects and 23 controls. The FT4I am/pm ratio was significantly higher in depressed subjects than in controls. This elevated diurnal ratio of thyroid hormones in depression adds to the literature on the chronobiology of affective disorders, and may help to explain differences in thyroid hormone levels in depressed patients in other studies, where time of sampling has seldom been reported.

Adolescent

Functional consequences of unilateral olfactory deprivation: time-course and age sensitivity.

Unilateral olfactory deprivation in the rat profoundly modifies olfactory bulb anatomy, chemistry and function. The present report examined the time-course of the functional effects of unilateral deprivation on inhibition in the olfactory bulb using paired-pulse stimulation of the lateral olfactory tract and olfactory nerve. In addition, an attempt was made to correlate these physiological measures with olfactory bulb dopamine and norepinephrine levels and tyrosine hydroxylase immunoreactivity. Deprivation from postnatal day 1 to postnatal day 20 or postnatal day 40 significantly enhanced lateral olfactory tract paired-pulse depression, while late onset deprivation (postnatal day 20) had no effect. Olfactory nerve paired-pulse depression was enhanced by 40 days of deprivation regardless of the age at onset. The time-course of these deprivation-induced physiological changes did not correlate well with reductions in dopamine. Dopamine levels were reduced in all deprivation conditions by 70-80% compared with control bulbs. Norepinephrine content was slightly elevated in deprived bulbs. These results suggest that early olfactory deprivation modifies olfactory bulb synaptic activity and further, as with other sensory systems, these effects are age and duration dependent.

Aging

Assessing school readiness through the school-entry screening exam.

Although there exists no perfect screening tool that is predictive of a child's success in school, an office visit prior to school enrollment can detect potential problems. This visit should include a history and physical, and developmental assessment. The developmental assessment involves a sampling of a child's abilities in the areas of language, reasoning, gross and fine motor skills, and personal-social development. Providers must be alert to signs and symptoms indicating impediments to learning. Clinicians who are knowledgeable about trends in education regarding readiness testing, birth-date cutoffs and retention can serve as a valuable resource to parents. The clinician can also be a major contributor to the achievement of national education goals set forth by the Bush administration. Ten tools for assessing children are compared, and their appropriate use is discussed.

Child

Brain abnormalities in male children and adolescents with hemophilia: detection with MR imaging. The Hemophilia Growth and Development Study Group.

Cranial magnetic resonance (MR) imaging was performed in 124 male patients (aged 7-19 years), from 14 institutions, in whom a diagnosis of moderate to severe hemophilia was made. Blood tests in all subjects were negative for human immunodeficiency virus. Findings in MR studies were abnormal in 25 (20.2%) subjects. Six lesions in five subjects were classified as congenital. The most commonly identified congenital lesion was a posterior fossa collection of cerebrospinal fluid (five cases). Twenty-two subjects had acquired lesions that were probably related to the hemophilia or its treatment. The most commonly acquired lesions were single- or multifocal areas of high signal intensity within the white matter on T2-weighted images noted in 14 (11.3%) subjects. Two subjects had large focal areas of brain atrophy, and six had some degree of diffuse cerebral cortical atrophy. Three subjects (2.4%) had hemorrhagic lesions. To the authors' knowledge, the unexpected finding of small, focal, nonhemorrhagic white matter lesions has not previously been reported.

Adolescent

Mechanisms regulating neurohypophysial blood flow and function during isotonic volume expansion.

Regional cerebral and neurohypophysial blood flow responses to isotonic extracellular fluid volume expansion were studied in pentobarbital-anesthetized dogs using radiolabeled microspheres. Measurements were made at baseline and after increasing pulmonary capillary wedge pressure by 8 +/- 2 mmHg. Plasma arginine vasopressin (AVP) decreased by 50%, and neural lobe blood flow (NLBF) decreased by 47%. Blood flow through median eminence and other brain regions was unchanged. We investigated potential mechanisms responsible for the NLBF changes. Following control vagotomy, AVP concentration increased during the first hour and then returned to control values for hours 2 and 3, whereas NLBF was unchanged for the first hour and fell after 2 and 3 h. Vagus section abolished the decrease in NLBF but not the AVP response to volume expansion. The contribution of left atrial and pulmonary baroreceptors to this response was tested by inflation of a balloon in the left atria to produce a 13 +/- 1 mmHg rise in atrial pressure. This led to a 20% reduction in NLBF, a 35% reduction in AVP concentration, and a 270% increase in plasma atrial natriuretic factor (ANF). However, ANF release does not account for the NLBF changes, since intravenous ANF infusion had no effect on NLBF or AVP concentration. These data suggest that the NLBF response to volume expansion is mediated by the vagus with input from multiple cardiopulmonary baroreceptors.

Animals

Effects of graded hypotension on cerebral blood flow, blood volume, and mean transit time in dogs.

This study tested the hypothesis that cerebral blood flow (CBF) is maintained by vasodilation, which manifests itself as a progressive increase in mean transit time (MTT) and cerebral blood volume (CBV) when cerebral perfusion pressure is reduced. Cerebral perfusion pressure was decreased in 10 pentobarbital-anesthetized dogs by controlled hemorrhage. Microsphere-determined CBF was autoregulated in all tested cerebral regions over the 40- to 130-mmHg cerebral perfusion pressure range but decreased by 50% at approximately 30 mmHg. MTT and CBV progressively and proportionately increased in the right parietal cerebral cortex over the 40- to 130-mmHg cerebral perfusion pressure range. Total hemoglobin content (Hb1), measured in the same area by an optical method, increased in parallel with the increases in CBV computed as the (CBF.MTT) product. At 30 mmHg cerebral perfusion pressure, CBV and Hb were still increased and MTT was disproportionately lengthened (690% of control). We conclude that within the autoregulatory range, CBF constancy is maintained by both increased CBV and MTT. Outside the autoregulatory range, substantial prolongation of the MTT occurs. When CBV is maximal, further reductions in cerebral perfusion pressure produce disproportionate increases in MTT that signal the loss of cerebral vascular dilatory hemodynamic reserve.

Animals

Neural mechanisms regulating neurohypophysial resistance arteries.

We defined the extent of vasoactive intestinal polypeptide (VIP) and noradrenergic influences on isolated 100- to 200-microns-diameter vessels from the resistance arterial circulation of the neurohypophysis. A dual extracranial (inferior hypophysial) and intracranial (superior hypophysial) arterial supply to the neurohypophysis was confirmed. The inferior hypophysial artery demonstrates noradrenergic and VIP-like perivascular nerves, whereas the superior hypophysial artery shows primarily VIP-like innervation. Pharmacological sensitivity of the inferior hypophysial to VIP [mean effective dose (ED50) = 10(-8.2) M] and to norepinephrine (ED50 = 10(-5.7) M) was demonstrated. The superior hypophysial reacted only to VIP (ED50 = 10(-8.6) M). The physiological relevance of these findings was tested with transmural nerve stimulation. Frequency-dependent vasodilation of both inferior and superior hypophysial arteries was demonstrated. This dilation could not be blocked with atropine or propranolol. Frequency-dependent vasoconstriction was identified in extracranial vessels including the inferior hypophysial artery. This constriction is only partially blocked by prazosin, phentolamine, and guanethidine. When neurohypophysial resistance vessels are compared with larger circle of Willis arteries and similar-size pial vessels of other cerebral regions, they appear to have regionally unique neural mechanisms for regulating blood flow. Specifically whether controlled by periarterial nerves or other tissue influences, the inferior hypophysial artery appears to meet anatomic, pharmacological, and physiological definitions of neural control for both dilator and constrictor activities of flow to the neurohypophysis.

Animals

Salmonella typhimurium abscess as a postoperative complication in a horse with colic.

An 11-year-old, 430-kg fox-trotter stallion was referred for evaluation of colic. A right-sided inguinal hernia was diagnosed. At exploratory laparotomy, the ileum was found to be herniated through the right inguinal canal. Compromised small intestine was resected, jejunocecal anastomosis was performed, and the horse was castrated. Three days after surgery, the stallion would not bear weight on the left hind limb. The musculature of the left thigh region became swollen. Aspiration of the left thigh region yielded serosanguineous fluid from which Salmonella typhimurium was isolated. Ultrasonography of the left thigh revealed multiple hypoechoic areas suggestive of abscess. The left medial thigh region was surgically incised, and a large abscess was drained. Bacteriologic culture of feces yielded S typhimurium. The owner elected to have the horse euthanatized.

Abscess

Clinical and morphometric analysis of the hypoplastic corpus callosum.

A total of 307 children were evaluated over a 3-year period in our neurogenetics clinic. Review of their medical records demonstrated 26 patients with diagnoses of anomalies of the corpus callosum. Morphometric analysis was performed on those 23 patients qualitatively assessed as having a hypoplastic (small, but morphologically intact) corpus callosum. Morphometric data were compared with clinical correlates for each patient. From these data, we conclude that the hypoplastic corpus callosum is not a normal variant of development but rather an indicator of a more fundamental abnormality of cerebral development.

Agenesis of Corpus Callosum

Nifedipine pharmacokinetics and pharmacodynamics during the immediate postpartum period in patients with preeclampsia.

Pharmacokinetic and pharmacodynamic parameters of oral nifedipine were studied in the immediate postpartum period in eight women with preeclampsia. Peak serum concentrations of 18 +/- 2.1 micrograms/L occurred 40 minutes after ingestion of nifedipine (10 mg). The terminal elimination half-life (mean = 1.35 +/- 0.3 hours) was found to be shorter than that reported for normotensive volunteers or nonpregnant hypertensive women (mean, 3.4 +/- 0.4 hours). A mean apparent oral elimination clearance of 3.3 +/- 1.3 L/hr/kg was more rapid than that found in normal volunteers (mean, 0.49 +/- 0.09 L/hr/kg) or in women with pregnancy-induced hypertension in the third trimester (mean, 2.0 +/- 0.8 L/hr/kg). Initial nadirs in mean arterial pressure were noted at 50 minutes after ingestion of nifedipine, with an average reduction in mean arterial pressure of 13.8 mm Hg. A dosing interval of every 3 to 4 hours is suggested when rapid-release nifedipine is used in the postpartum patient with preeclampsia.

Administration, Oral

Neural correlates of conditioned odor avoidance in infant rats.

Newborn rat pups can learn to either approach or avoid odor cues through associative conditioning. The present results demonstrate that preference conditioning and avoidance conditioning both modify olfactory bulb responses (focal 2-deoxyglucose uptake and mitral-tufted cell single unit responses) to the conditioned odor. Despite opposing behavioral responses to the conditioned odor, however, olfactory bulb neural responses did not detectably differ between learned odor cues signaling approach and those signaling avoidance. Control pups exhibited neither the behavioral nor neural changes. Furthermore, both the behavioral and neural changes to these odor cues could be extinguished. These results suggest that the olfactory bulb in neonates may code learned odor importance, but specific information attached to that importance may require processing in other brain regions.

Animals

Olfactory associative conditioning in infant rats with brain stimulation as reward: II. Norepinephrine mediates a specific component of the bulb response to reward.

One of the circuits modified by early olfactory learning is in the olfactory bulb. Specifically, response patterns of mitral-tufted cells are modified by associative conditioning during the early postnatal period. In addition, previous work has demonstrated that mitral-tufted cell single units respond to both olfactory conditioned stimuli and rewarding stimulation of the medial forebrain bundle-lateral hypothalamus (MFB-LH). The present study suggests that norepinephrine beta-receptor activation is required for early olfactory learning using MFB-LH stimulation as reward. Propranolol injected before odor-MFB-LH pairings blocks the acquisition of conditioned behavioral responses and their neural correlates to the conditioned odor. Furthermore, propranolol blocks a specific class of the mitral-tufted cell responses to MFB-LH reward stimulation. The relationship of this response to reward and early learning is discussed.

Aging

Transient white matter changes on MR images in children undergoing chemotherapy for acute lymphocytic leukemia: correlation with neuropsychologic deficiencies.

The cranial magnetic resonance (MR) images of 25 children with acute lymphocytic leukemia (ALL) who were undergoing chemotherapy were retrospectively studied to determine the frequency of white matter changes and to analyze the significance of these observed changes in predicting subsequent neuropsychologic deficiencies. MR images showed transient white matter abnormalities in 17 of the 25 patients during consolidation therapy. Twelve of 20 children showed neuropsychologic deficits. There was no correlation between white matter changes and neuropsychologic deficits. In the subgroup of children under age 5 years at the time of diagnosis, 10 of 11 showed neuropsychologic deficits, and eight of 11 had white matter changes. Children under age 5 who undergo chemotherapy for ALL are at high risk to develop neuropsychologic deficiencies. Age at diagnosis is a reliable predictor of subsequent neuropsychologic deficits.

Adolescent

Atlantoaxial malformation in a half-Arabian colt.

A 1-year-old half-Arabian colt was referred for evaluation of a cranial cervical abnormality. Physical examination revealed the left wing of the atlas to be more ventral than the right wing. A head tilt, with the pole deviated to the left, was present because of the malpositioned atlas. Neurologic examination identified symmetrical weakness, ataxia, and proprioceptive deficits in all four limbs. Radiographs of the cranial cervical region revealed fusion of the atlas and axis, and deviation of the atlantoaxial joint to the left of the median plane. Euthanasia was elected. Necropsy confirmed the radiographic findings. The atlas was rotated 20 degrees counterclockwise when viewed from the caudal aspect. Multifocal myelomalacia was present in the first and second cervical spinal cord segments. The malformation was believed to be due to a degenerative process or abnormal embryological development.

Animals