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Biomedical subjects

R M Cohen

Publications and source records attributed to R M Cohen.

At least 145 records · Page 8Linked to original sources
PubMed1987

Intravenous methylprednisolone efficacy in status asthmaticus of childhood.

Forty-nine nonsteroid-dependent children hospitalized with status asthmaticus were randomized to receive IV placebo or methylprednisolone treatment (1 mg/kg every six hours). All patients received nebulized isoetharine inhalations and continuous IV aminophylline infusion. Twenty-four hours after admission, the methylprednisolone-treated patients demonstrated a greater rate of improvement in their clinical scoring index than did placebo-treated children. However, the duration of hospital stay was not significantly shortened. Twenty-eight of the patients performed serial bedside spirometry at 0, 12, 24, and 36 hours after admission. The methyl-prednisolone-treated patients experienced a more rapid recovery from peripheral airway obstruction as measured by forced expiratory flow rate during 25% to 75% of forced vital capacity (FEF25-75). The magnitude and rate of improvement in FEF25-75 was significantly greater at 36 hours (P less than .05) and independent of changes in peak expiratory flow rate, forced vital capacity, or forced expiratory volume in the first second of forced vital capacity. Placebo-treated patients had a higher incidence of asthma relapse within 4 weeks of discharge (eight v two relapses, P less than .05). Findings of this study indicate that IV corticosteroid therapy is beneficial in treating pediatric status asthmaticus.

Adolescent↗
PubMed1987

Lipid cell tumor of the ovary in reference to adult-onset congenital adrenal hyperplasia and polycystic ovary syndrome. A case report.

A 30-year-old woman with a virilizing lipid tumor was initially suspected of having adult-onset congenital adrenal hyperplasia (CAH) when her plasma 17-hydroxyprogesterone (17OHP) concentration was found to be very high (298-3,170 ng/dL), to drop in response to an overnight dexamethasone (dex) suppression test (79 ng/dL) and to rise briskly 15 minutes after ACTH administration (751 ng/dL). However, the effect of dex was not sustained or complete: the pregnanetriol excretion dropped only from 5.5 to 4.4 mg daily. Furthermore, the plasma testosterone was inappropriately high (235-537 ng/dL) for adult-onset CAH and was more responsive to endogenous and exogenous gonadotropin stimulation than to ACTH. In addition, there was no evidence of 11 beta-hydroxylation of 21-deoxycorticoids, as would be expected in CAH. Removal of the tumor completely reversed the virilization and the abnormal responses to ACTH and human chorionic gonadotropin. The contralateral ovary bore lipid-laden stromal cells in the deep paracortex that bore a striking resemblance to the tumor cells, and a cyst in that ovary had fluid with a steroid pattern virtually identical to that of the tumor, with an androstenedione: 17OHP ratio of 5:1. There was not evidence of polycystic ovary disease. The clinical picture of type II polycystic ovary syndrome (PCOS) gradually evolved over a one-year period postoperatively: plasma-free testosterone became mildly elevated and was not dex suppressible. The 17OHP response to ACTH became slightly excessive. However, there was no evidence of tumor on computed tomography.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1986

The effects of glutaraldehyde cross-linking on the function of the adenylate cyclase complex of turkey erythrocytes.

Glutaraldehyde appears to preferentially effect the activation processes of the adenylate cyclase complex of turkey erythrocyte membranes. The primary effect of low concentration (0.01 percent, 0.05 percent, and 0.1 percent) glutaraldehyde membrane treatment is to decrease catecholamine-stimulated cAMP formation. The effect can be blocked by prior activation of the system with isoproterenol + p[NH]ppG. 0.6 percent glutaraldehyde treatment of membranes has substantial effects on both F(-)- and catecholamine-stimulated cAMP production. The effects are blocked by prior activation of the adenylate cyclase complex with NaF, but not by isoproterenol + p[NH]ppG. Glutaraldehyde at these concentrations has no effect on Mn++-stimulated cAMP formation. The data is discussed with respect to the organization of the major macromolecular components of the adenylate cyclase complex as it exists within the native membrane prior to and following activation of the system.

Adenylyl Cyclases↗
PubMed1986

Naloxone and Alzheimer's disease. Cognitive and behavioral effects of a range of doses.

There have been conflicting reports on the effects of naloxone hydrochloride in patients with dementia of the Alzheimer type (DAT). In addition, none of the naloxone studies in DAT used doses of 2.0 mg/kg or more, the amount necessary to produce reliable cognitive and behavioral changes in young normal subjects. In a randomized, double-blind, placebo-controlled study, 12 patients with DAT were administered naloxone hydrochloride in doses of 5 micrograms/kg, 0.1 mg/kg, and 2.0 mg/kg, with detailed evaluation of its behavioral and cognitive effects using measures selected for their potential relevance to DAT and the known effects of blockade of endogenous opiate systems. None of the measures of motor performance, attention, memory, learning, or recognition showed improvement with naloxone. Increased inappropriate verbal productions were noted after 0.1 mg/kg of naloxone hydrochloride. Patients became irritably activated after this dose, which may account for the altered verbal behavior in this study and also for some of the changes suggesting cognitive improvement in prior studies. Differences in the sensitivity and dose dependency of the behavioral effects in patients with DAT compared with prior studies in young normal subjects merit further investigation.

Adult↗
PubMed1986

Proinsulin radioimmunoassay in the evaluation of insulinomas and familial hyperproinsulinemia.

Two new radioimmunoassays for human proinsulin (hPI) have been developed and used to study patients with islet cell tumors and familial hyperproinsulinemia. Both antisera were adsorbed against human C-peptide conjugated to Sepharose, following which cross-reactivity to insulin and C-peptide was less than 0.001%. Antiserum 18D recognized the junction between the insulin B-chain and C-peptide and provided fivefold greater sensitivity than our previously reported hPI assay. Antiserum 11E recognized a determinant which includes or is adjacent to the A-chain-C-peptide junction or which is specified by the tertiary structure. In all 20 patients studied with surgically confirmed islet cell tumors, fasting plasma proinsulinlike material (PLM) was abnormal (greater than 3 SD from the mean measured in either lean or obese subjects) in both assays. This provided better discrimination than has been reported for PLM measured by gel filtration (abnormal in 13 of 14 of the present samples) with a considerably less laborious procedure. Samples from two families in which a mutant proinsulin is present in the circulation have immunoreactivity in the two assays consistent with previous identification of the molecule as an A-chain-C-peptide-linked intermediate of proinsulin conversion. The immunoreactivity of a sample from another family in which large amounts of proinsulin circulate are consistent with an intact molecule being the predominant form. This assay will be useful for confirming the diagnosis of insulin-secreting tumor in patients suspected of recurrent fasting hypoglycemia and in physiologic studies of proinsulin secretion.

Adenoma, Islet Cell↗
PubMed1986

Effect of chronic treatment with clorgyline on the relative concentration of specific proteins in the hippocampus and parietal cortex of the rat.

The effect of the chronic administration of clorgyline, a type A inhibitor of monoamine oxidase, on the relative concentration of proteins from the brain of the rat was examined by analysis of two-dimensional electrophoretic gels. The results from this study showed that the administration of clorgyline for 3 weeks produced a significant elevation in the relative concentration of two proteins in the parietal cortex (mol. wt 23,000 and 30,000) and one protein in the hippocampus (mol. wt 25,000). In contrast, the relative concentration of three proteins (mol. wt 31,000, 42,000 and 45,000) was significantly reduced in the parietal cortex by chronic treatment with clorgyline. No protein in the hippocampus was found to be significantly reduced by treatment with clorgyline. Since a previous study has indicated that the relative concentration of three different proteins were significantly altered by the repeated administration of desipramine, the results from the present experiment indicate that different changes in proteins are produced by repeated treatment with the type A monoamine oxidase inhibitor, clorgyline, as compared to those produced by the tricyclic antidepressant, desipramine. These results support previous suggestions that different classes of antidepressant compounds may exert their effects through different mechanisms of action.

Animals↗
PubMed1986

Foot shock induces time and region specific adrenergic receptor changes in rat brain.

Rats were subjected to 1 hr or 2 hr of electric foot shock for 1 day or 7 days and adrenergic receptor binding was evaluated in the hypothalamus, brainstem and cortex. beta-Adrenergic receptor density in the hypothalamus was dramatically reduced following 1 hr of shock. Following repeated shock, alpha 2-adrenergic receptors in the cortex and brainstem were observed to increase. Cortical alpha 2-adrenergic receptors were more sensitive to stress than the alpha 2-adrenergic receptors of the brainstem, alterations in the latter only reaching statistical significance following 7 days of shock and 24 hr of recovery. alpha 1- and beta-adrenergic receptors in the brainstem and cortex were relatively resistant to stress induced changes. The significance of type of stress, duration of stress, and strain of rat for understanding the current data are discussed in the context of prior reports of stress induced receptor changes.

Adaptation, Physiological↗
PubMed1986

Human plasma melatonin is elevated during treatment with the monoamine oxidase inhibitors clorgyline and tranylcypromine but not deprenyl.

Melatonin was measured in plasma collected between 8:00 and 8:30 a.m. from 27 depressed patients studied before and after 21- to 24-day treatment with three monoamine oxidase (MAO) inhibitors. Baseline plasma melatonin concentrations determined by radioimmunoassay were 4.0 +/- SD 4.7 pg/ml. Tranylcypromine, a nonselective MAO inhibitor given in doses of 20-40 mg/day for 3 weeks, significantly elevated plasma melatonin to 10.6 +/- SD 2.0 pg/ml. Clorgyline, given in doses of 15-30 mg/day for 3 weeks, produced a significant, approximately three-fold increase in plasma melatonin (13.6 +/- SD 13.5 pg/ml). This clorgyline dose was selective for MAO type A inhibition, as MAO-B activity measured in platelets from the same blood samples was unaffected by clorgyline. In contrast, the selective MAO-B inhibitor deprenyl (10-30 mg/day for 3 weeks) led to a 96 +/- 4% inhibition of platelet MAO-B activity but no significant change in plasma melatonin (5.1 +/- SD 4.2 pg/ml). As both serotonin and norepinephrine are preferentially metabolized by MAO-A rather than MAO-B, an increased availability of serotonin (the precursor of melatonin) or enhanced noradrenergic function might mediate the melatonin changes observed to follow MAO-A but not MAO-B inhibition.

Blood Platelets↗
PubMed1986

Pharmacologic modelling of Alzheimer's disease.

Evidence pointing to the central role of the cholinergic system in normal human memory function and disorders such as Alzheimer's disease has grown tremendously in recent years. Anticholinergic and non-cholinergic agents have been found to create transient memory impairments in young adults which mimic the changes associated with normal aging or amnesia. The rationale for using scopolamine, a centrally active anticholinergic agent, as a pharmacologic probe of memory function is reviewed using data from studies in animals and humans. The cognitive functioning of normal elderly controls given scopolamine is compared to the baseline functioning of patients with Alzheimer's disease, followed by a discussion of the use of scopolamine as a modelling agent for dementia.

Adult↗
PubMed1986

Design and interpretation of opiate antagonist trials in dementia.

In view of the reports of possible beneficial effects of naloxone in dementia, rationales and strategies for studying endogenous opiate systems are reviewed. Important considerations in the design and interpretation of clinical investigations using naloxone are also reviewed. The nature and distribution of endogenous opiate systems are summarized from an historical perspective. Endogenous opiate systems are distributed throughout the central nervous system and play important roles in a variety of brain functions, including memory and learning. In view of this, several rationales are evident for studying endogenous opiate systems in dementia, since it is a syndrome in which structures known to contain opiate systems are disturbed, functions modulated by opiate systems are disturbed, and other neurotransmitter systems (functionally linked to endogenous opiate systems) are disturbed. Different strategies for studying endogenous opiate systems are reviewed, including examination of body fluids and pharmacologic challenge studies. Naloxone hydrochloride, a competitive opiate receptor antagonist, is a commonly used pharmacologic agent. The design of a multidose naloxone study of 12 dementia patients is discussed, with reference to the pharmacokinetics, pharmacodynamics, and specificity of naloxone as well as to the nature of the dependent measures selected for this study. No cognitive benefit was observed in this study. Behavioral arousal was observed at naloxone doses, with more evident psychomotor retardation at higher doses. These findings are contrasted with the results of naloxone challenges in other studies. The varying effects of naloxone within and across populations can be conceptualized in terms of the basic and clinical considerations previously discussed. The importance of dose-finding studies is stressed for this and other drug trials.

Alzheimer Disease↗
PubMed1986

Syntheses and D2 receptor affinities of derivatives of spiperone containing aliphatic halogens.

The development of a high affinity dopamine receptor ligand labeled with the positron emitting radionuclide, 18F (t 1/2 = 110 min), is of considerable interest for imaging and quantification of dopamine receptors in vivo. Derivatives of spiperone, a dopamine antagonist, labeled with 18F have been prepared, but the syntheses either proceed with inefficient fluoride utilization or involve several synthetic steps subsequent to 18F incorporation. To date, only the short-lived radioisotope of carbon, 11C (t 1/2 = 20.4 min), has been efficiently incorporated in the final synthetic step of 3-N-[11C]methyl-spiperone. 3-N-Fluoroethyl, 3-N-chloroethyl, and 3-N-bromoethyl spiperone derivatives are prepared by alkylation of spiperone with the appropriate 2-tosyloxy ethyl halide. In addition, alpha-fluorospiperone, containing fluorine alpha to the butyrophenone carbonyl, has been prepared. The 3-N-haloethyl spiperones display high affinity for dopamine receptor in vitro. Incorporation of [18F]fluoride during the final synthetic step yields a high affinity, 18F-labeled dopamine receptor-binding ligand.

Animals↗
PubMed1986

Differential sensitivity of "central" and "peripheral" type benzodiazepine receptors to phospholipase A2.

The effects of preincubating cerebral cortical membranes with phospholipase A2 (PLA2) were examined on radioligand binding to benzodiazepine receptors of the "central" and "peripheral" types. PLA2 (0.005-0.1 U/ml) increased [3H]flunitrazepam and [3H]3-carboethoxy-beta-carboline binding by increasing the apparent affinities of these ligands with no concomitant change in the maximum number of binding sites. In contrast, neither gamma-aminobutyric acid (GABA)-enhanced [3H]flunitrazepam binding nor [3H]Ro 15-1788 binding was altered by preincubation with PLA2 at concentrations as high as 2 U/ml. Both pyrazolopyridine (SQ 65,396)- and barbiturate (pentobarbital)-enhanced [3H]flunitrazepam binding and [35S]t-butylbicyclophosphorothionate (TBPS) binding were markedly reduced by as little as 0.0025-0.005 U/ml of PLA2. These findings suggest that PLA2 inactivates the TBPS binding site on the benzodiazepine-GABA receptor chloride ionophore complex, which results in a selective loss of allosteric "regulation" between the components of this complex. PLA2 also reduced the apparent affinity of [3H]Ro 5-4864 to peripheral-type benzodiazepine receptors in cerebral cortical, heart, and kidney membranes, but increased the number of [3H]PK 11195 binding sites with no change in apparent affinity. These data demonstrate that PLA2 can differentially affect the lipid microenvironment of "central" and "peripheral" types of benzodiazepine receptors.

Animals↗
PubMed1986

In vivo deactivation of proinsulin action on glucose disposal and hepatic glucose production in normal man.

We have studied the deactivation of the in vivo actions of insulin and biosynthetic human proinsulin (recombinant DNA) to stimulate the glucose disposal rate (GDR) and to inhibit hepatic glucose output (HGO) in man. Twelve healthy, lean, young subjects were studied using a modification of the euglycemic glucose clamp technique. Subjects received 4-h infusions on separate occasions of insulin (15 mU/m2/min equivalent to 0.54 microgram/m2/min) or proinsulin (2.75 micrograms/m2/min), achieving steady-state serum levels of 32 +/- 3 microU/ml (equivalent to 0.23 +/- 0.02 pmol/ml) and 3.7 +/- 0.2 pmol/ml, respectively. Suppression of HGO was similar (83-84%) with proinsulin and insulin, but stimulation of GDR above basal was greater with insulin (3.41 +/- 0.43 versus 1.98 +/- 0.28 mg/kg/min, P less than 0.001). Following cessation of the hormone infusions, serum proinsulin concentration fell in a biphasic fashion with half-times of 25 and 146 min for the two phases. Serum half-disappearance time for insulin was 5 min. Deactivation of the hormone's effects to stimulate GDR was 50% complete by 35 min after insulin and 71 min after proinsulin. In contrast, 50% of the recovery times for the effect on suppression of HGO were 55 min after insulin and 188 min after proinsulin. Serum glucagon levels did not differ significantly after the insulin and proinsulin infusions. In summary: (1) Deactivation of proinsulin and insulin's effects to suppress HGO proceeds more slowly than deactivation of their effects to stimulate GDR; and (2) There is a markedly prolonged and disproportionately delayed deactivation of proinsulin's effects on suppression of HGO. This later finding may prove of therapeutic value in the treatment of diabetes mellitus.

Adult↗
PubMed1986

Positron emission tomography.

PET is a unique tool for the direct in vivo evaluation of physiologic processes within discrete areas of the brain. Thus far, its application to the study of schizophrenia has served to confirm the subtleties of this illness. However, PET does promise to increase our knowledge of the neurochemical anatomy of the normal and abnormal mind with respect to goal-directed behavior.

Basal Ganglia↗