PubMed Health⌕ Search

Biomedical subjects

D P Friedman

Publications and source records attributed to D P Friedman.

At least 19 recordsLinked to original sources
PubMed2001

Progression of changes in dopamine transporter binding site density as a result of cocaine self-administration in rhesus monkeys.

The present study examined the time course of alterations in levels of dopamine transporter (DAT) binding sites that accompany cocaine self-administration using quantitative in vitro receptor autoradiography with [(3)H]WIN 35,428. The density of dopamine transporter binding sites in the striatum of rhesus monkeys with 5 d, 3.3 months, or 1.5 years of cocaine self-administration experience was compared with DAT levels in cocaine-naive control monkeys. Animals in the long-term (1.5 years) exposure group self-administered cocaine at 0.03 mg/kg per injection, whereas the initial (5 d) and chronic (3.3 months) treatment groups were each divided into lower dose (0.03 mg/kg per injection) and higher dose (0.3 mg/kg per injection) groups. Initial cocaine exposure led to moderate decreases in [(3)H]WIN 35,428 binding sites, with significant changes in the dorsolateral caudate (-25%) and central putamen (-19%) at the lower dose. Longer exposure, in contrast, resulted in elevated levels of striatal binding sites. The increases were most pronounced in the ventral striatum at the level of the nucleus accumbens shell. At the lower dose of the chronic phase, for example, significant increases of 21-42% were measured at the caudal level of the ventral caudate, ventral putamen, olfactory tubercle, and accumbens core and shell. Systematic variation of cocaine dose and drug exposure time demonstrated the importance of these factors in determining the intensity of increased DAT levels. With self-administration of higher doses especially, increases were more intense and included dorsal portions of the striatum so that every region at the caudal level exhibited a significant increase in DAT binding sites (20-54%). The similarity of these findings to previous studies in human cocaine addicts strongly suggest that the increased density of dopamine transporters observed in studies of human drug abusers are the result of the neurobiological effects of cocaine, ruling out confounds such as polydrug abuse, preexisting differences in DAT levels, or comorbid psychiatric conditions.

Animals↗
PubMed2001

Chronic cocaine-mediated changes in non-human primate nucleus accumbens gene expression.

Chronic cocaine use elicits changes in the pattern of gene expression within reinforcement-related, dopaminergic regions. cDNA hybridization arrays were used to illuminate cocaine-regulated genes in the nucleus accumbens (NAcc) of non-human primates (Macaca fascicularis; cynomolgus macaque), treated daily with escalating doses of cocaine over one year. Changes seen in mRNA levels by hybridization array analysis were confirmed at the level of protein (via specific immunoblots). Significantly up-regulated genes included: protein kinase A alpha catalytic subunit (PKA(calpha)); cell adhesion tyrosine kinase beta (PYK2); mitogen activated protein kinase kinase 1 (MEK1); and beta-catenin. While some of these changes exist in previously described cocaine-responsive models, others are novel to any model of cocaine use. All of these adaptive responses coexist within a signaling scheme that could account for known inductions of genes(e.g. fos and jun proteins, and cyclic AMP response element binding protein) previously shown to be relevant to cocaine's behavioral actions. The complete data set from this experiment has been posted to the newly created Drug and Alcohol Abuse Array Data Consortium (http://www.arraydata.org) for mining by the general research community.

Animals↗
PubMed2001

Fellowship and practice trends in neuroradiology training programs in the United States.

BACKGROUND AND PURPOSE: Neuroradiology has become an increasingly diverse and subspecialized discipline. We evaluated the current status and trends affecting fellowship programs and the practice of clinical neuroradiology at academic medical centers, with emphasis on invasive procedures. METHODS: All 85 program directors at Accreditation Council for Graduate Medical Education-approved fellowships in neuroradiology were sent a detailed questionnaire pertaining to various demographic aspects of their program and the performance of certain radiologic examinations of the brain and spine. RESULTS: Sixty-seven programs (79%) responded. As many as 50% of programs are 1 year in length. Twenty-five percent of 2-year fellows leave their program after 1 year of training. During the past 5 years, 36% of programs have decreased in size and 73% reported a decline in the number of applicants. The majority (55%) of programs have had applicants renege on their commitment to begin a fellowship. Twenty percent of 2-year programs do not offer training in endovascular interventional procedures. Neurosurgeons perform endovascular interventional procedures at 18% of centers. There is an 18-fold variation in the volume of neuroangiographic procedures performed each year and a 150-fold variation in the volume of myelographic procedures performed. In 29% of programs, neuroradiologists are nonparticipants in nonvascular interventional spinal procedures; in 40%, they share these procedures with musculoskeletal radiologists/nonradiologists. CONCLUSION: Interest in fellowship programs in neuroradiology is declining. An applicant's commitment to either begin a fellowship or complete 2 years of training cannot be regarded with assurance, and there is a lack of uniformity in many areas of the training experience, particularly in invasive diagnostic and therapeutic procedures.

Central Nervous System Diseases↗
PubMed1999

Stereotactic radiosurgical pallidotomy and thalamotomy with the gamma knife: MR imaging findings with clinical correlation--preliminary experience.

PURPOSE: To evaluate the temporal evolution and appearance of a radiosurgical lesion at magnetic resonance (MR) imaging and the clinical response in patients undergoing stereotactic radiosurgical pallidotomy or thalamotomy with the gamma knife. MATERIALS AND METHODS: Seventeen patients with medically refractory movement disorders underwent stereotactic radiosurgical pallidotomy (n = 2) or thalamotomy (n = 15). A single dose of 120-140 Gy was administered to a target in the globus pallidus interna or ventralis intermedius thalamic nucleus. Postprocedure gadolinium-enhanced MR imaging and clinical assessment were performed at 1 month and 3 months. RESULTS: At 3 months, the radiosurgical lesion most commonly (n = 11) appeared as a ring-enhancing focus 5 mm or less in diameter surrounded by vasogenic edema that extended less than 7 mm in radius beyond the target. Five patients had ring-enhancing lesions 7 mm or more in diameter; four of these developed symptomatic perilesional edema at 3 (n = 2) or 8 (n = 2) months after the procedure. Onset of therapeutic effect began approximately 4 weeks after treatment. In the 15 patients with tremor, there was a mean decline of 2.1 on the Tremor Rating Scale. CONCLUSION: Findings in this pilot study suggest that radiosurgical thalamotomy is a promising treatment for medically refractory tremor. Three-month follow-up MR studies show a ring-enhancing lesion surrounded by a variable amount of vasogenic edema. Visualization of the radiosurgical lesion and the clinical response are delayed compared to that with radio-frequency procedures.

Adult↗
PubMed1999

The relationship between the functional abilities of patients with cervical spinal cord injury and the severity of damage revealed by MR imaging.

BACKGROUND AND PURPOSE: The appearance of the damaged spinal cord after injury correlates with initial neurologic deficit, as determined by the American Spinal Injury Association grade and manual muscle test score, as well as with recovery, as assessed by manual muscle test scores. The purpose of this study was to determine whether the presence of spinal cord hemorrhage and the size and location of spinal cord edema on MR images is predictive of functional recovery in survivors of cervical spinal cord injury (SCI). METHODS: The degree of damage to the cervical spinal cord was measured on the MR images of 49 patients who underwent imaging within 72 hours of sustaining SCI. The effects of hemorrhage and length/location of edema on changes in the value of the motor scale of the functional independence measure (FIM) were assessed on admission to and discharge from rehabilitation. RESULTS: Patients without spinal cord hemorrhage had significant improvement in self-care and mobility scores compared with patients with hemorrhage. There was no significant effect of spinal cord hemorrhage on changes in locomotion and sphincter control scores. The rostral limit of edema positively correlated with admission and discharge self-care scores and with admission mobility and locomotion scores. Edema length had a negative correlation with all FIM scales at admission and discharge. CONCLUSION: The imaging characteristics of cervical SCI (hemorrhage and edema) are related to levels of physical recovery as determined by the FIM scale. Imaging factors that correlate with poor functional recovery are hemorrhage, long segments of edema, and high cervical locations.

Activities of Daily Living↗
PubMed1998

Angiotensin-(1-7) immunoreactivity in the hypothalamus of the (mRen-2d)27 transgenic rat.

The distribution of angiotensin-(1-7) immunoreactive neurons was compared to those of vasopressin-(VP) and oxytocin-(OT) immunoreactive (IR) neurons in the hypothalamus of adult (mRen-2d)27 transgenic hypertensive and Sprague-Dawley rats. In both strains, angiotensin (Ang)-(1-7)-IR cells were found in the supraoptic nucleus (SON), and in the anterior (ap-), medial (mp-), and lateral (lp-) parvocellular, and posterior magnocellular (pm-) subdivisions of the paraventricular (PVN) nucleus. Three-dimensional reconstructions showed that cells immunoreactive to Ang-(1-7) and VP were specifically co-distributed in the SON and in the pmPVN. Double-labeling neurons for both peptides revealed that both Ang-(1-7) and VP were colocalized in a subpopulation of neurons in the pmPVN and SON. In combination with previous studies, our results suggest that Ang-(1-7) and VP are colocalized, co-released and may have a combined action at a common target. In addition, the introduction of the mouse submandibular renin (mRen-2d) transgene into Sprague-Dawley rats does not appear to have altered the fundamental organization of hypothalamic peptide systems involved in fluid homeostasis.

Angiotensin I↗
PubMed1998

Effect of cocaine self-administration on striatal dopamine D1 receptors in rhesus monkeys.

An array of evidence indicates that long-term exposure to cocaine alters several components of the brain dopamine system. Because the release of dopamine in the nucleus accumbens (NAc) has been implicated in mediating the reinforcing effects of cocaine, changes in dopamine function can have profound effects on drug-seeking and drug-taking behavior. The present study examined the effects of the chronic self-administration of cocaine on the D1 family of dopamine receptors in the rhesus monkey. The brains of three rhesus monkeys that had intravenously self-administered an average of 1.35 mg/kg cocaine per day for 18-22 months were compared to the brains of three cocaine-naive controls. The in vitro quantitative autoradiographic technique was used to quantify binding densities of the D1 ligand [3H]SCH-23390 on cryostat-cut sections of fresh frozen tissue. In animals that self-administered cocaine, the density of D1 binding was significantly lower in the regions of the striatum at the level where the nucleus accumbens is most fully developed. The shell of the NAc showed the largest difference with significantly lower D1 binding also detected in adjacent regions of the caudate nucleus and the putamen. No differences were found in the rostral pole of the NAc or the dorsal striatum at that level. These findings suggest that chronic self-administration of cocaine can modulate the density of dopamine D1 receptors in specific portions of the primate striatum. Such changes might underlie some of the behavioral consequences, like drug dependence and craving, of long-term cocaine use.

Animals↗
PubMed1998

Effect of cocaine self-administration on dopamine D2 receptors in rhesus monkeys.

The present study used autoradiography to examine the effects of chronic self-administration of cocaine on the density of dopamine D2 receptors in nonhuman primates. Three rhesus monkeys intravenously self-administered an average of 1.35 mg/kg cocaine per day for 18-22 months until they were euthanized immediately after a self-administration session. Binding site density of the D2 ligand [3H]raclopride (2 nM) was assessed in these monkeys as well as three untreated controls, using quantitative in vitro receptor autoradiography. As compared to untreated controls, D2 binding site density was significantly lower in the animals that self-administered cocaine in all regions of the striatum rostral to the anterior commissure. These regions include the anterior and central regions of the caudate nucleus, putamen, olfactory tubercle, and both the shell and core of the nucleus accumbens. Within the substantia nigra and ventral tegmental area, by contrast, no differences were found in the density of D2 binding sites. These findings suggest a pervasive effect of cocaine on the regulation of D2 receptors in the striatum. The lack of change within the ventral midbrain, however, suggests a differential regulation of D2 receptors in the striatum and ventral midbrain. This study confirms and extends our knowledge of the neurobiological changes in the mesolimbic dopamine system that result from chronic exposure to cocaine.

Animals↗
PubMed1997

Enhanced MR imaging of hypertrophic pachymeningitis.

OBJECTIVE: This report illustrates the contrast enhancement characteristics on MR imaging of three patients with hypertrophic pachymeningitis and provides an explanation for the observed imaging findings. CONCLUSION: A differential pattern of enhancement, consisting of intense enhancement of the peripheral margin of the abnormal pachymeninges, was present in all cases. In two patients, much of the remaining abnormal pachymeninges did not enhance at all. On the basis of the microscopic pathology of hypertrophic pachymeningitis, the physiology of normal meningeal enhancement on MR imaging, and the described MR appearance of other pachymeningeal lesions, this differential pattern of enhancement should strongly suggest the diagnosis of hypertrophic pachymeningitis.

Adult↗
PubMed1996

Cocaine alters cerebral metabolism within the ventral striatum and limbic cortex of monkeys.

The functional consequences of acute cocaine administration in nonhuman primates were assessed using the quantitative 2-[14C]deoxyglucose method. Local rates of cerebral metabolism were determined after an intravenous infusion of 1.0 mg/kg cocaine or vehicle in six awake cynomolgus monkeys (Macaca fascicularis) trained to sit calmly in a primate chair. Cocaine administration decreased glucose utilization in a discrete set of structures that included both cortical and subcortical portions of the limbic system. Glucose metabolism in the core and shell of the nucleus accumbens was decreased markedly, and smaller decrements were observed in the caudate and anterior putamen. In addition, cocaine administration produced significant decreases in limbic cortex. Metabolism was decreased in orbitofrontal cortex (areas 11, 12o, 13, 13a, 13b), portions of the gyrus rectus including area 25, entorhinal cortex, and parts of the hippocampal formation. The cortical regions in which functional activity was altered provide dense projections to the nucleus accumbens, and the decreased activity in these projections may be responsible in part of the large alterations in functional activity within the ventral striatum. Decreased metabolism also was evident in the anterior nuclear group of the thalamus, raphe nuclei, and locus ceruleus. The acute cerebral metabolic effects of cocaine in the conscious macaque, therefore, were contained primarily within a set of interconnected limbic regions, including ventral prefrontal cortex, medial temporal regions, the ventral striatal complex, and anterior thalamus. The decreased rates of glucose metabolism reported here resemble decrements found using positron emission tomography in humans. In the rat, by contrast, metabolic activity increased and changes were focused in subcortical regions. The present results represent an important expansion of the neural circuitry on which cocaine acts in the monkey as compared with the rat, and this in turn implies that cocaine affects a broader spectra of behaviors in primates than in rodents.

Animals↗
PubMed1996

Performance of neuroradiologic examinations by nonradiologists.

PURPOSE: To determine the level of participation by nonradiologists in performing neuroradiologic examinations. MATERIALS AND METHODS: Medicare part B claims data from fiscal year 1992 were analyzed for CPT (current procedural terminology) codes related to computed tomography (CT) and magnetic resonance (MR) imaging of the brain, head and neck, and spine, as well as myelography, angiography, and diskography. Data were tabulated by place of service (hospital-based vs freestanding imaging centers) and by medical specialty. RESULTS: Among 363,224 Medicare claims for CT and MR imaging of the brain, head and neck, and spine, 91% of the examinations were performed in hospitals and 9% in offices or freestanding centers; 98% of studies were interpreted by a radiologist. The largest share of radiology billing by nonradiologists was from office-based or freestanding imaging centers (9%), versus 2% at hospital-based facilities. CONCLUSION: Radiologists perform the vast majority of neuroradiologic examinations. Most neuroradiologic examinations performed by nonradiologists are from neurologists at freestanding/office-based imaging centers.

Angiography↗
PubMed1996

Forecasting motor recovery after cervical spinal cord injury: value of MR imaging.

PURPOSE: To determine whether magnetic resonance (MR) imaging quantification of cervical spinal cord damage improves the prediction of motor recovery after spinal cord injury. MATERIALS AND METHODS: The extent of cervical spinal cord injury was measured on MR images obtained in 104 patients (aged 17-70 years) within 72 hours of spinal cord injury. The effects of hemorrhage and edema length on motor outcome were examined for at least 12 months. RESULTS: Patients with spinal cord hemorrhage had significantly lower upper and lower extremity motor scores at the time of injury and at 12 months than did patients without hemorrhage (P < .001). There was little recovery of lower extremity function even in patients without hemorrhage. Upper extremity motor function improved significantly in all patients (P < .001); patients without hemorrhage showed the largest improvements. The motor recovery rates for patients without hemorrhage were 0.74 (upper extremities; range, 0-1) and 0.55 (lower extremities; range, 0-1); those for patients with hemorrhage were 0.31 (range, 0-1) and 0.091 (range, 0-1). Stepwise multiple regression analyses indicated that MR information on hemorrhage and the length of edema increases the ability to predict clinical outcome by 16%-33% over that with initial clinical scores alone. CONCLUSION: An initial MR imaging evaluation of the spinal cord after spinal cord injury provides supplemental prognostic information on the recovery of motor function in the upper and lower extremities.

Adolescent↗