Biomedical subjects

R C Saunders

Publications and source records attributed to R C Saunders.

At least 37 records · Page 2Linked to original sources

PubMed1997

Quantification of amphetamine-induced changes in [11C]raclopride binding with continuous infusion.

Positron emission tomography and single-photon emission computer tomography receptor-binding ligands can be used to measure changes in neurotransmitter levels. In particular, amphetamine-induced dopamine release has been assessed with [11C]raclopride by paired bolus injections and with [123I]iodobenzamide by using a single bolus plus infusion (B/I) study. Here, we measured the change in [11C]raclopride-specific binding in rhesus monkeys after i.v. administration of 0.4 mg/kg amphetamine by using both the bolus and B/I paradigms. Paired bolus studies (control and postamphetamine) were analyzed using compartment modeling and graphical analysis with a new plasma metabolite model to measure the total distribution volume (VT). Specific binding, calculated with three measures linearly proportional to the binding potential, demonstrated a 22-42% reduction in the postamphetamine study. VT values from B/I studies were determined by the tissue-to-plasma ratio at equilibrium, in addition to the bolus methods. There was good agreement between the control VT values between bolus and B/I studies. The amphetamine-induced change in specific binding in B/I studies was 19 +/- 16%, measured directly from tissue radioactivity levels. This study demonstrates that stimulus-induced changes in specific binding can be measured with a single [11C]raclopride study using the B/I method.

Amphetamine↗

PubMed1997

Kinetic modeling of [11C]raclopride: combined PET-microdialysis studies.

The in vivo binding of D2 receptor ligands can be affected by agents that alter the concentration of endogenous dopamine. To define a more explicit relation between dopamine and D2 receptor binding, the conventional compartment model for reversible ligands has been extended to account for a time-varying dopamine pulse. This model was tested with [11C]raclopride positron emission tomography and dopamine microdialysis data that were acquired simultaneously in rhesus monkeys. The microdialysis data were incorporated into the model assuming a proportional relation to synaptic dopamine. Positron emission tomography studies used a bolus-plus-infusion tracer delivery with amphetamine given at 40 minutes to induce dopamine release. The extended model described the entire striatal time-activity curve, including the decrease in radioactivity concentration after an amphetamine-induced dopamine pulse. Based on these results, simulation studies were performed using the extended model. The simulation studies showed that the percent decrease in specific binding after amphetamine measured with the bolus-plus-infusion protocol correlates well with the integral of the postamphetamine dopamine pulse. This suggests that changes in specific binding observed in studies in humans can be interpreted as being linearly proportional to the integral of the amphetamine-induced dopamine pulse.

Animals↗

PubMed1997

Effects of inferior temporal lesions on two types of orientation discrimination in the macaque monkey.

Rhesus monkeys with transection of the forebrain commissures were trained in two different tasks in which grating orientation was the discriminandum. In the temporal same-different task, the monkeys had to judge whether or not two successively presented gratings differed in orientation. In the identification task, we measured how well the monkey could judge the orientation of the grating. The performance in any task was affected neither by a unilateral anterior temporal cortical area lesion nor by a subsequent posterior temporal cortical area lesion in the same hemisphere resulting in a two-stage inferior temporal (IT) lesion. However, a single stage IT (combined anterior and posterior temporal cortical areas) lesion of the other hemisphere severely disrupted the performance in the temporal same-different task, but only barely increased just noticeable differences in orientation in the identification task. This indicates that the impairment in a temporal comparison task after an IT lesion is not due to a perceptual coding deficit, but is related to the temporal comparison per se. Thus, IT is involved in the temporal comparison of successively presented stimuli. On the other hand, the two IT lesions, each having a different history (single versus two stage) had dramatically different behavioural effects, suggesting an important role for adult brain plasticity in determining the behavioural outcome of a brain lesion.

Animals↗

PubMed1996

Mental health services utilization in a children's mental health managed care demonstration.

Service delivery under two systems of care--a traditional Civilian Health and Medical Program of the Uniformed Services (CHAMPUS) reimbursement system and an innovative continuum of care--was examined along six dimensions: access, type, mix, volume, timing, and continuity of services received by children and adolescents. It was found that the Demonstration served over three times as many children as the Comparison. In addition to serving more children, the Demonstration also provided more and different types of services to each child treated. Finally, the Demonstration appears to have delivered services in a more timely fashion and made a considerable effort to match children's and families' needs with services.

Adolescent↗

PubMed1996

The costs of mental health services under the Fort Bragg Demonstration.

This article examines the costs of treatment under the Fort Bragg Demonstration. It focuses on the direct costs of mental health services and suggests that expenditures on those services were much higher at the Demonstration. Increased access and greater "doses" of services provided at the Demonstration are identified as the proximal causes of the system-level cost difference. Consideration is given to whether these differences in costs and in service use can be attributed to the continuum of care per se or to differences in the financial arrangements under which care was provided. Supplemental analyses suggest that these expenditures were not offset by cost savings elsewhere. Implications for mental health policy are discussed.

Adolescent↗

PubMed1995

Lesions of the superior temporal cortical motion areas impair speed discrimination in the macaque monkey.

The effects of circumscribed lesions of the superior temporal cortical motion areas on speed discrimination were tested in three macaque monkeys using both moving random-textured patterns and moving bars. The lesions, which included the middle temporal visual area, the adjacent medial superior temporal visual area and the fundus superior temporal visual area, produced a severe and lasting deficit in speed discrimination when tested with the random patterns. In contrast, deficits were smaller when tested with moving bars. Control lesions of the inferior temporal cortex in two monkeys had little effect on speed discrimination. There was no clear deficit following inferior temporal or superior temporal sulcus lesions on a vernier acuity task. These experiments indicate that the middle temporal and adjacent areas play a crucial role in speed discrimination and that lesion effects depend on the cues available to the animals.

Animals↗

PubMed1995

Autoradiographic characterization of neurotensin receptors in the entorhinal cortex of schizophrenic patients and control subjects.

Neurotensin, an endogenous peptide and putative neurotransmitter, exhibits a wide range of interactions with dopaminergic neurons and displays some actions akin to neuroleptics. Moreover, neurotensin receptors are abundant in specific layers of the entorhinal cortex where cytoarchitectural abnormalities have been reported in schizophrenia. We therefore examined the entorhinal cortex from postmortem specimens of five control patients and six schizophrenic patients for alterations in neurotensin receptor quantitation and distribution using receptor autoradiography. Specific 125I- neurotensin binding was concentrated in layer II cell clusters, with a 40% reduction in binding in the schizophrenic group (p < 0.05). Moderate binding was observed in both cohorts in deep layers V/VI, with negligible binding in the hippocampus. There was no statistical difference in quantitative neurotensin binding in other lamina of the entorhinal cortex of schizophrenics compared with controls. The characteristic laminar pattern of binding did not differ between cohorts. The reduction in neurotensin binding in schizophrenics is consistent with an increasing number of reports of structural abnormalities in the medial temporal lobe of schizophrenics in general and the entorhinal cortex in particular. Further studies are required to examine the evidence for neuroanatomic and neurochemical pathology in the entorhinal cortex.

Adult↗

PubMed1995

Augmentation of prefrontal cortical monoaminergic activity inhibits dopamine release in the caudate nucleus: an in vivo neurochemical assessment in the rhesus monkey.

Prefrontal cortical modulation of caudate nucleus dopamine release was investigated in the rhesus monkey using the in vivo microdialysis technique. Reliable and stable basal caudate nucleus dopamine levels were quickly attained within hours following insertion of the dialysis probes. High-potassium (60 mM) or tetrodotoxin (10 microM) infusions significantly altered caudate nucleus dopamine levels in the dialysate indicating that measured dopamine levels reflected impulse-dependent release from the presynaptic pool. Pharmacological augmentation of monoaminergic transmission in the sulcus principalis region of the prefrontal cortex resulted in significant alterations in caudate nucleus dopamine levels. Increase of monoaminergic activity by infusion of either D-amphetamine (100 microM) or cocaine hydrochloride (100 microM) resulted in a gradual and prolonged decrease in caudate nucleus dopamine levels. Similar decreases were noticed in caudate nucleus dopamine metabolite levels. The present results indicate that in non-human primates modulation of dorsolateral prefrontal cortical monoaminergic transmission results in alterations in dopamine levels in subcortical structures. This observation may have clinical implications for therapeutic management of certain neuropsychiatric disorders, particularly schizophrenia.

Amphetamine↗

PubMed1994

Local pharmacological manipulation of extracellular dopamine levels in the dorsolateral prefrontal cortex and caudate nucleus in the rhesus monkey: an in vivo microdialysis study.

The prefrontal cortex, caudate nucleus, and their dopaminergic innervations have been implicated in complex information processing. The present study utilized the in vivo microdialysis technique to characterize the extracellular dopamine levels in the prefrontal cortex and the caudate nucleus in the rhesus monkey. Basal levels of dopamine were consistently found in the caudate nucleus, while levels in the prefrontal cortex were less reliably measured. Manipulation of dopamine levels using tetrodotoxin and high potassium demonstrated that dopamine measured was dependent on neuronal firing. Administration of indirect dopamine agonists d-amphetamine and cocaine into the prefrontal cortex and the caudate nucleus increased extracellular dopamine levels 250% and 5000%, respectively. Amphetamine and cocaine had greater effects on dopamine levels in the caudate than in the prefrontal cortex. Cocaine induced increases appeared to be less than that of amphetamine and the actions of cocaine lasted longer than amphetamine. This study demonstrates the feasibility of using in vivo microdialysis in monitoring neurochemicals in different regions of the rhesus monkey brain.

Animals↗

PubMed1994

Hemispheric lateralization in rhesus monkeys can be task-dependent.

Two rhesus monkeys with transection of the forebrain commissures were trained on two grating orientation-discrimination tasks. In one task, the simultaneous orientation identification task, monkeys had to decide which of two simultaneously presented gratings was horizontal. In the other task, the temporal same-different task, the monkey had to decide whether or not two successively presented gratings differed in orientation. Both monkeys showed a statistically significant individual asymmetry in the performance on the same-different task with the left hemisphere supporting superior performance compared with the right hemisphere. No such consistent lateralization was found for the identification task. These results show that the demonstration of a behavioral asymmetry depends on the type of discrimination task performed and suggest that the asymmetry is related to interhemispheric differences in higher order stimulus (cognitive) processing and not to a lateralization of early visual processes.

Animals↗

PubMed1994

An improved methodology for routine in vivo microdialysis in non-human primates.

A new method was developed to carry out in vivo microdialysis experiments repetitively and routinely within an individual monkey. We designed and built a dialysis probe guide and holding device ('guide holder') which permits accurate placement of dialysis probes into cortical (e.g., prefrontal, hippocampus, and parietal cortices) and subcortical target areas (e.g., caudate nucleus, amygdala, and nucleus accumbens) of the rhesus monkey brain without extensive and repetitive surgery needed to expose a desired brain region. The guide holder is positioned, using MRI-guided coordinates, and fixed to the skull over an intended targeted region. This design provides an opportunity to conduct several experiments in a single monkey over an extended period and permits placement of several probes accurately into 'fresh' or 'experienced' tissue during repeated microdialysis experiments. In addition, during repeated dialysis experiments tissue trauma is minimized because no surgical procedure is necessary on the day of dialysate collection. This procedure can be readily adapted for use with an awake monkey.

Animals↗

PubMed1994

Autoradiographic characterization of 125I-neurotensin binding sites in human entorhinal cortex.

The laminar and rostro-caudal distribution of 125I-neurotensin binding sites is described in human entorhinal cortex using quantitative autoradiography. Specific binding was most prominent over the cell clusters of layer II of the entorhinal cortex throughout its rostro-caudal extent. Dense binding was also observed in the adjacent presubiculum and cortical amygdaloid transition area, whereas minimal binding was detected in the hippocampus and dentate gyrus. 125I-Neurotensin may serve as a selective probe for neurotensin receptor alterations and layer II-specific cytoarchitectural disturbances in the entorhinal cortex in neuropsychiatric diseases associated with abnormalities of the mesial temporal lobe.

Adult↗

PubMed1994

Antenatal diagnosis of choledochal cyst.

We report five infants in whom antenatal diagnosis of choledochal cyst was established by ultrasonography, and we review the seven previously reported cases. All but one infant had cystic dilatation of the common bile duct (type 1 cysts), and all infants were diagnosed during the second or third trimester. Eight of 12 infants (67%) developed jaundice in the first few days of life, but only 25% had a palpable abdominal mass. Seven of nine infants (78%) demonstrated complete obstruction of the distal common bile duct on intraoperative cholangiography. Liver histology was available for six patients. Five of six had cirrhosis or fibrosis with bile duct proliferation. All of the infants with fibrosis or cirrhosis had distal common bile duct obstruction. Despite liver biopsy findings of extensive fibrosis plus ascites with failure to thrive in one of our patients, all five patients demonstrated clinical and biochemical improvement following surgical excision and porto- or choledochoenterostomy. All were free of symptoms by 6 months of age. Congenital choledochal cyst should be considered in the differential diagnosis of any sonolucent abdominal mass of the fetus. Neonates with distal common bile duct obstruction and fibrosis in association with presumed choledochal cyst should have prompt surgical exploration, intraoperative cholangiography, and close postoperative follow-up. The long-term outcome with prompt surgical correction is excellent.

Choledochal Cyst↗

PubMed1993

Repair of cranial defects with teflon: a method of cranioplasty in monkeys.

Magnetic resonance imaging demonstrated the need for cranioplasty in experimental neurobehavioral studies with non-human primates. Postoperatively temporal lobes showed substantial deformation of the neocortex due to pressure from the overlying muscle. A new method of cranioplasty using teflon to cover a cranial defect has been developed. Teflon is easily shaped and fitted into place. This method is safe, allows for the natural shape of the brain, provides protection, and is compatible with imaging techniques. Cranioplasty with teflon should be considered whenever craniotomy is necessary for accessing the brain.

Animals↗

PubMed1993

Posterior extensile approach to the elbow joint and distal humerus.

Between 1986 and 1990, the authors treated 14 intra-articular fractures of the distal humerus using a posterior extensile approach. This approach, a combination of a triceps-splitting approach and an olecranon osteotomy, allows extensive exposure of the posterior aspect of the elbow joint and distal humerus, facilitating fracture reduction. The extensile approach is advocated for intra-articular fractures of the distal humerus with proximal extension. This approach can be extended proximally to the midshaft of the humerus or distally to expose the radial head and the ulnar shaft. The anatomy of the radial nerve and the innervation of the triceps were noted by studying 10 cadaveric elbow specimens.

Adult↗

PubMed1992

Effects of inferotemporal cortex lesions on form-from-motion discrimination in monkeys.

The inferotemporal cortex of primates plays a prominent role in the learning and retention of visual form discriminations. In this experiment we investigated the role of inferotemporal (IT) cortex in the discrimination of two-dimensional forms defined by motion cues. Six monkeys were trained to a criterion level of performance on two form-from-motion problems. Three of these animals received complete bilateral lesions of IT cortex, while the other three served as unoperated controls. All animals were then retrained to criterion to evaluate the effects of IT lesions on the retention of form-from-motion learning. Compared with the control group, the lesion group was significantly impaired on both problems. Following retention testing, we trained both groups of monkeys on two new form-from-motion problems to investigate the effects of IT lesions on acquisition rates for new learning. The lesion group performed well on the new problems; the learning rates of the operated and control groups were not significantly different. When forms were defined by luminance cues, monkeys with IT lesions, like those in previous studies, were impaired both for retention and for acquisition. These findings indicate that the anterograde effects of IT lesions on learning new form discriminations are less severe for forms defined by motion cues than for forms defined by luminance cues. However, the retrograde effects of IT lesions on retention are severe for forms defined by either cue.

Animals↗

PubMed1990

Magnetic resonance imaging of the rhesus monkey brain: use for stereotactic neurosurgery.

Standard stereotactic procedures rely upon external cranial landmarks and standardized atlases for localization of subcortical neural regions. Magnetic resonance imaging permits the visualization of the neural structure of the brain in vivo. A stereotactic instrument compatible with a magnetic resonance unit was constructed and together with magnetic resonance imaging a procedure was developed that overcomes the limitations and inaccuracies of the traditional stereotactic methods and allows accurate and reliable localization of subcortical targets in the rhesus monkey brain.

Animals↗

PubMed1990

Methodology of microdialysis of neostriatum in hemiparkinsonian nonhuman primates.

In vivo biochemical microdialysis in primate brain would greatly expand our understanding of functional neuronal systems. This work describes our efforts to establish a microdialysis system in primate brain. Seven anesthetized rhesus monkeys underwent magnetic resonance imaging (MRI) with the head fixed in a compatible stereotaxic frame. This allowed stereotaxic localization of the caudate nucleus and putamen. Guide cannulae were implanted and fixed to the skull. Microdialysis probes made from polyethylene and fused silica were inserted into the caudate and putamen through the guide cannulae and perfused at the rate of 1.3 microliters/min. The putamens were approached horizontally, while the caudate nuclei were reached via a 30 degrees-45 degrees angle from the vertical. Postdialysis MRI and histologic evaluation proved that all probes accurately arrived at the predetermined region. Our data show that MRI guided stereotaxis allows accurate placement of dialysis probes and that implantation of guide cannulae is a reliable and convenient way to perform repeated brain microdialysis procedures.

Animals↗