Hospital admission and benzodiazepine use.
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Benzodiazepines↗
Biomedical subjects
R M Cohen
Publications and source records attributed to R M Cohen.
Failure to activate the left temporoparietal cortex in dyslexia. An oxygen 15 positron emission tomographic study.
To test the hypothesis of left temporoparietal dysfunction in dyslexia, suggested by neuropsychological and neuropathologic data, cerebral blood flow was measured with positron emission tomography in 14 right-handed men with severe developmental dyslexia (mean [SD] age, 27 [5] years; median reading level, fifth grade) and 14 matched controls at rest and during an auditory phonologic task (rhyme detection) and an auditory attention task involving the detection of target tones. As expected, normal readers activated left temporoparietal cortex during rhyme detection but not during the nonphonologic attentional task. Dyslexic men failed to activate those left temporoparietal regions activated in controls during rhyme detection but did not differ from controls in these regions during rest or attentional testing. Thus, the expected left temporoparietal dysfunction was demonstrated only when specific probes for these regions were employed.
Adult↗
Preliminary data on the metabolic brain pattern of patients with winter seasonal affective disorder.
The brain metabolic pattern of patients with winter seasonal affective disorder with and without light treatment was determined by positron emission tomography. Compared with controls, patients with seasonal affective disorder with and without light treatment had globally lower metabolic rates, relatively lower superior medial frontal cortex rates, and somewhat higher basal ganglia rates. Patients receiving light treatment had a relatively higher rate in an occipital region of interest containing the primary visual cortex. Patients without light treatment had relatively higher metabolic rates in right parietal and medial orbitofrontal cortex and lower rates in the left parietal cortex. Patients not receiving light treatment had a hemispheric metabolic asymmetry (left greater than right) for the midprefrontal cortex located 67 mm above the canthomeatal line. The right side of this region, previously found reduced in manic-depressive illness and schizophrenia, was decreased primarily in patients with seasonal affective disorder with fewer atypical depressive symptoms. These "abnormal" prefrontal and parietal cortex regions appeared highly "coupled" in the patients with seasonal affective disorder.
Adult↗
Metabolic brain pattern of sustained auditory discrimination.
Positron emission tomography of [18F]-2-fluorodeoxyglucose was used to assess the functional brain activity of normal subjects while performing auditory discrimination (CPT), while receiving an identical set of tones as in CPT, but with the instructions that they were background noise, or while at rest. The present study: (1) confirms earlier findings of an association between the functional activity of the right midprefrontal cortex and the performance of auditory discrimination, (2) localizes this increase in right prefrontal cortex activity to the middle prefrontal gyrus; and (3) provides a framework of specific testable hypotheses for the evaluation of the importance of certain limbic and paralimbic areas in the biological determination of sustained attention to be addressed in future studies. The framework accounts for the now confirmed finding that the middle cingulate has lower metabolic activity in CPT than at rest, and new findings of alterations in temporal lobe processing of tones in response to attention.
Acoustic Stimulation↗
Direct detection of Molluscum contagiosum virus in clinical specimens by in situ hybridization using biotinylated probe.
Molluscum contagiosum virus (MCV) is an unclassified poxvirus which has recently become recognized as causing a major sexually transmitted disease. At present no assay is available for specific detection of MCV because the virus cannot be serially propagated in cell culture. Since MCV produces an abortive, limited growth with some cytopathic effect in certain cell lines, we were able to develop an in situ hybridization assay for detection of MCV genome in clinical specimens. Human fetal diploid lung cell monolayers were infected with clinical specimens, and after proper incubation and fixation in paraformaldehyde, hybridization was performed under full stringency conditions with a molecularly cloned biotinylated probe. Only MCV infected cells showed homology to the MCV probe with a purple-brown cytoplasmic staining. Additionally, we have described an in situ hybridization assay for direct detection of MCV genome in formalin-fixed, paraffin-embedded biopsies. Characteristic intracytoplasmic Molluscum bodies (Henderson-Paterson bodies) were detected in stratum spinosum cells of the epidermis. Striking staining similarities have been observed between in situ hybridization and haematoxylin-eosin cytostaining. These procedures are the first successful identification of MCV genome in clinical samples by molecular hybridization, with sensitivity and specificity equal to or greater than electron microscopy.
Blotting, Southern↗
Positron emission tomography with 18F-dopa: interpretation and biological correlates in nonhuman primates.
Positron emission tomography (PET) was carried out, with 18F-DOPA as a ligand, in normal control monkeys and "parkinsonian" monkeys who had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The following approaches were used in data analysis: ratio of 18F accumulation in specific to nonspecific brain areas and 18F-DOPA influx constant obtained using either the actual plasma 18F-DOPA or the 18F activity in a nonspecific brain area as the input function. The results from these analyses were compared to one another and to biological parameters relevant to dopaminergic function. The striatum/cortex ratio and the rate constant calculated from plasma 18F-DOPA appeared to be the most sensitive analytic techniques.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Hypoglycemia with hyperinsulinemia in a chronic hemodialysis patient following parathyroidectomy.
We report a chronic hemodialysis patient with severe hyperparathyroidism who developed hypoglycemia with inappropriate hyperinsulinemia following parathyroidectomy. An abrupt fall in parathyroid hormone level and administration of large amounts of calcitriol may have resulted in increased insulin release and enhanced tissue sensitivity to insulin producing sustained hypoglycemia in this patient.
Calcitriol↗
Regional cerebral glucose metabolism in bulimia nervosa.
OBJECTIVE: The authors' purpose in this study was to further delineate the character of cerebral metabolism in bulimia nervosa and to determine if functional links could be made between regional cerebral metabolism and the symptoms of depression, obsessive-compulsive disorder, and bulimia nervosa. METHOD: Regional cerebral glucose metabolism was measured by using positron emission tomography in 11 inpatients with bulimia nervosa and 18 normal comparison subjects matched in sex (all were women), age, and educational level. The bulimic patients were also tested for symptoms of major depression and obsessive-compulsive disorder. RESULTS: The patients with bulimia showed a correlation between lower left anterolateral prefrontal regional cerebral glucose metabolism and greater depressive symptoms. However, the orbitofrontal regional cerebral glucose metabolism of patients with bulimia was not greater than that of comparison subjects, nor was higher orbitofrontal metabolism correlated with greater obsessive-compulsive disorder symptoms. CONCLUSIONS: These findings lead to the conclusion that left anterior lateral prefrontal cortex hypometabolism varies with the depressive symptoms observed in bulimia but that temporal lobe hypermetabolism and asymmetries appear to be independent of the mood state.
Adult↗
Descriptions of psychiatric conditions in literature.
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Humans↗
Hyperproinsulinemia in type II diabetes.
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Cross Reactions↗
Human retinal vascular cells differ from umbilical cells in synthetic functions and their response to glucose.
Cell culture systems have commonly been used to study mechanisms implicated in the pathogenesis of diabetic retinopathy, but the great majority of cell preparations used have been either of nonhuman retinal origin or nonretinal human origin. Because of questions of species and organ specificity in the function of cells of vascular origin, in this study, cultured microvascular endothelial cells (HREC), pericytes (HRPC), and pigment epithelial cells from the postmortem human retina, and endothelial cells from human umbilical vein (HUVEC) were evaluated with respect to cell proliferation, and secretory products potentially important in diabetic retinopathy, i.e., prostaglandins (PG) and plasminogen activators (PA), normalized to DNA content/well, under both basal (5 mM) and high (25 mM) glucose conditions. Glucose (25 mM) reduced DNA content similarly in both types of endothelial cells, had a lesser effect on HRPC, and did not significantly alter the proliferation of pigment epithelial cells. Basal secretion of PGI2 (measured as 6-keto-PGF1 alpha) was in the order HRPC much greater than HREC greater than HUVEC, whereas PGE2 secretion was in the order HREC much greater than HRPC greater than HUVEC. Glucose (25 mM) stimulated PGI2 secretion by HRPC, but not by either type of endothelial cell, and enhanced PGE2 secretion by HREC, but not by HUVEC or HRPC. Release of plasminogen activator activity differed between HUVEC and HREC under basal conditions and addition of 25 mM glucose stimulated release only from HREC. Glucose (25 mM) stimulated PA secretion by HREC, but not by HUVEC. These findings provide evidence that human retinal pericytes are an important source of prostacyclin, and that there are differences between HREC and HUVEC with respect to secretory functions and their modulation by glucose, indicating regional specificity of these functions. Extrapolation to human retinal vascular cells from experiments using cells from heterologous vascular beds to draw inferences about the pathophysiology of diabetic retinopathy are not valid for these cellular functions.
Adult↗
Cerebral glucose metabolism in patients with summer seasonal affective disorder.
Positron emission tomography scans of nine patients diagnosed with summer seasonal affective disorder (SSAD) were compared with scans of 45 normal control subjects to investigate differences in brain glucose metabolism. All subjects performed an auditory discrimination task beginning several minutes before injection of F-18-deoxyglucose and continuing for 30 minutes after injection. Regional glucose metabolic rates were extracted from 60 rectangular regions of interest measured in five planes selected as atlas matches from 28 total slices. Statistically significant differences between patients with SSAD and normal control subjects were found in cerebral glucose metabolic rate and also in normalized regional glucose metabolic rates in the orbital frontal cortex and in the left inferior parietal lobule.
Adult↗
A controlled trial of recombinant human erythropoietin and nandrolone decanoate in the treatment of anemia in patients on chronic hemodialysis.
We conducted a prospective, randomized study in chronic hemodialysis patients in order to determine whether the erythropoietic response to low dose recombinant human erythropoietin (rHuEpo) could be enhanced by administration with androgens. Patients received rHuEpo 40 U/kg intravenously three times weekly either alone (Group 1, n = 6) or with weekly intramuscular injection of 2 mg/kg nandrolone decanoate (Group 2, n = 6) for up to 16 weeks. Baseline hct, ferritin, N-terminal parathyroid hormone, and aluminum levels were similar. The mean weekly rate of rise in hct was 0.32 +/- 0.13% in Group 1 and 0.37 +/- 0.11% in Group 2, p = NS. Three of 6 patients in Group 1, but only 1 of 6 patients in Group 2, reached the target hct of 30% within 16 weeks. Two patients in Group 2 requested that the nandrolone decanoate be stopped prior to reaching target hct because of unacceptable side effects (acne). We conclude that many chronic hemodialysis patients appear to respond adequately to rHuEpo at the dose used in our study. Nandrolone decanoate does not enhance the response rate to this rHuEpo dose and is associated with significant side effects.
Anabolic Agents↗
Delayed L-phenylalanine infusion allows for simultaneous kinetic analysis and improved evaluation of specific-to-nonspecific fluorine-18-dopa uptake in brain.
The accumulation of 3-O-methyl-6-[18F]fluoro-L-DOPA (18F-30M-DOPA) in the brain from the circulation is responsible for most of the nonspecific background during 18F-DOPA positron emission tomography scanning. To increase the sensitivity of 18F-DOPA for imaging presynaptic dopamine systems, we took advantage of 18F-30M-DOPA's rapid clearance from the brain (T1/2 approximately 15-20 min). The infusion of the unlabeled amino acid L-phenylalanine, starting 75 min after 18F-DOPA administration, prevents 18F-30M-DOPA entrance into the brain through competition at the large amino acid transport system of the blood brain barrier. This method produces high specific-to-nonspecific contrast images of 18F accumulation beginning 15-30 min after onset of amino acid infusion and better sensitivity to small changes in 18F-DOPA uptake while still allowing for kinetic analysis of the data in the early time points. Kinetic and anatomical data were found to be strongly correlated.
Animals↗
Reduced cerebrospinal fluid dynorphin A1-8 in Alzheimer's disease.
Cerebrospinal fluid (CSF) measures of dynorphin A were compared in three groups. Alzheimer patients (n = 9), elderly depressives (n = 9), and age-matched normal controls (n = 9). The Alzheimer patients revealed a 40% decrease in CSF dynorphin compared with controls (36 +/- 15 versus 60 +/- 21 pg/ml, p less than 0.05). In contrast, other peptide measures [Neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and galanin] remained unchanged across groups. This finding was further supported when an additional 20 Alzheimer patients with similar clinical backgrounds also showed reduced CSF dynorphin (37 +/- 13 pg/ml). CSF dynorphin did not correlate significantly with clinical variables or other CSF measures of monoamine metabolites [i.e., 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA)]. Given the previous report of increased kappa binding of Alzheimer brains at autopsy, the authors speculate about a possible up-regulation of opiate receptors in Alzheimer's disease and suggest ways to test this hypothesis in vivo.
Aged↗
Human growth hormone stimulates proliferation of human retinal microvascular endothelial cells in vitro.
Growth hormone (GH) has been implicated in the pathogenesis of proliferative diabetic retinopathy. We sought to determine whether this could be mediated by an effect of GH on proliferation of endothelial cells, and, for this purpose, established long-term cultures of human retinal microvascular endothelial cells (hREC) from normal postmortem human eyes. High-purity (greater than 95%) hREC preparations were selected for experiments, based on immunofluorescence with acetylated low density lipoprotein (LDL) and anti-factor VIII-related antigen. Growth requirements for these cells were complex, including serum for maintenance at slow growth rates and additional mitogens for more rapid proliferation. Exposure of hREC to physiologic doses of human GH (hGH) resulted in 100% greater cell number vs. control (P less than 0.01) but could be elicited only in the presence of serum. When differing serum conditions were compared, hGH stimulated [3H]thymidine incorporation up to 1.6- to 2.2-fold under each condition and increased DNA content significantly in the presence of human, horse, and fetal calf serum. Depending on the culture conditions used, the threshold hGH concentration for significant stimulation of hREC proliferation was 0.4-4 micrograms/liter. In contrast, proliferation of human umbilical vein endothelial cells was not significantly altered by hGH added to concentrations as high as 200 micrograms/liter. In summary, hREC respond to physiologic concentrations of hGH in vitro with enhanced proliferation. This specific effect of GH on retinal microvascular endothelial cells supports the hypothesis of a role for GH in endothelial cell biology.
Cell Division↗
Plasma catecholamines and their metabolites in obsessive-compulsive disorder.
Plasma catecholamines and their metabolites were sampled in 13 medication-free patients with obsessive-compulsive disorder (OCD) and 29 normal controls. In addition to severe OCD symptoms, the patients had significantly higher anxiety, tension, and resting pulse rates than the controls. Nonetheless, mean plasma concentrations of norepinephrine (NE) and epinephrine (E), the catecholamine metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA), and the stress-related hormone cortisol did not differ between OCD patients and normal controls. When the patients and control populations were combined and average plasma NE and E levels calculated over 35 min, subjects with a higher mean NE output (greater than 1.1 pm/ml) had higher Profile of Mood States depression scores than subjects with a low NE output (less than 1.1 pm/ml). Altogether, these results indicate that elevated plasma catecholamine measures are not likely to be associated with the pathophysiology of OCD.
Adult↗
New rapid analysis method demonstrates differences in 6-[18F] fluoro-L-dopa plasma input curves with and without carbidopa and in hemi-MPTP lesioned monkeys.
Kinetic modeling of the PET tracer 6-[18F]fluoro-L-dopa ([18F]Dopa), used to measure presynaptic dopamine function, requires the accurate determination of the plasma input curve. We have developed a new method that uses alumina extraction preceded by cation and anion exchange resins to determine the parent compound, [18F]Dopa and its critical metabolite 3-O-methyl-6-[18F]fluoro-L-dopa. Using this method we found that carbidopa increases the plasma input of [18F]Dopa while decreasing the rate of metabolite formation, and that previous drug treatment can significantly effect [18F]Dopa metabolism.
Animals↗