Inside MDT and AMSCO (American Sterilizer Company). The CEOs speak out on manufacturing in the DRG era.
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California↗
Biomedical subjects
D Nelson
Publications and source records attributed to D Nelson.
Motivating middle managers. How to develop their mission potential.
Today's unstable healthcare environment is prompting not-for-profit hospitals to explore ways to preserve a fading altruistic posture. Holy Cross Hospital, Salt Lake City, sees middle management as a key to preserving a mission-oriented commitment to the delivery of healthcare. It is tapping the potential of its middle managers through a specialized management development program linked to mission objectives that attempts to assess and enhance individual abilities. The hospital formed a management development committee to identify several managerial characteristics that could have the greatest positive impact on preserving the hospital's mission objectives. The committee identified six major categories for focus: mission and philosophy; leadership style and influence; staffing, coaching, and developing employees; implementation functions; decision-making functions; and quality assurance issues. The hospital developed a self-assessment questionnaire for middle managers. As a self-evaluation tool, the questionnaire may not accurately represent each manager's specific level of knowledge, but it shows each manager's perceived needs and provides a basis for the development of instructional resources. It has also been useful in raising managers' consciousness of their performance.
Hospital Administrators↗
Type III membranoproliferative glomerulonephritis in primary Sjögren's syndrome.
Glomerulonephritis is a rare complication of primary Sjögren's syndrome. When glomerulonephritis does occur, it is usually due to membranous, focal proliferative, or membranoproliferative lesions. There have been fewer than 20 reported cases of glomerulonephritis in primary Sjögren's syndrome, only three of which have been membranoproliferative. We report a case of primary Sjögren's syndrome complicated by Type III membranoproliferative glomerulonephritis, a specific type of mesangiocapillary glomerulonephritis never before reported in this setting, and describe a clinical course terminating in rapidly progressive renal failure.
Aged↗
A transient rise in agalactosyl IgG correlating with free interleukin 2 receptors, during episodes of erythema nodosum leprosum.
The proportion of oligosaccharide chains on the Fc fragment of IgG which terminate with N-acetylglucosamine and not galactose (%GO) has previously been shown to be raised in rheumatoid arthritis (RA), Crohn's disease (CD) and tuberculosis (Tb), but to be normal in sarcoidosis (SA), and in both lepromatous and tuberculoid leprosy. However we have now studied %GO in sequential serum samples collected from lepromatous leprosy patients undergoing episodes of erythema nodosum leprosum (ENL). During ENL %GO is transiently raised, and this rise parallels an increase in circulating interleukin 2 receptors (IL-2R). These findings confirm that changes in T cell function occur during ENL. Moreover it appears that %GO rises when there is, simultaneously, T-cell-mediated tissue damage and an acute phase response (RA, CD, Tb, ENL), but not when there is an acute phase response without major T cell involvement, or chronic T cell activity alone (SA, and tuberculoid leprosy). We suggest therefore that %GO is an indicator of a type of T cell activity with broad immunopathological implications.
Acetylglucosamine↗
Decisions near the end of life.
Designing behavior change programs and evaluating their effects on patient care has been a persistent challenge in research on continuing medical education. The challenge becomes even more complex when we aim to change behaviors that are interactive and highly influenced by the formal and informal institutional context. The authors describe an interdisciplinary continuing education program in bioethics that is designed to effect just such behaviors. The program aims to help hospital and long-term care facilities improve their ability to resolve the ethical dilemmas inherent in terminal care decisions. Targeted to interdisciplinary groups of physicians, nurses, social workers, pastoral counselors, and administrators, Decisions Near the End of Life will provide strategies and tools for examining institutional policies and team practices as well as more traditional information, education, and skill building. The authors describe the program's rationale and design, and raise questions about the potential for developing interdisciplinary, action-oriented CME on other topics.
Decision Making↗
Myelin basic protein and magnetic resonance imaging for diagnosing radiation myelopathy.
The identification of radiation myelopathy using biochemical assays and imaging techniques has not previously been accomplished but has clear clinical application. Measurement of myelin basic protein (MBP) in the cerebrospinal fluid (CSF) and visualization of the spinal cord using magnetic resonance imaging (MRI) gives a potentially accurate diagnosis of radiation myelopathy. Female New Zealand white rabbits were irradiated to the thoracic spinal cord with single doses of 15-45 Gy. Animals receiving higher doses (greater than or equal to 22 Gy) generally demonstrated an early paresis (4-8 weeks) that temporarily improved, and then progressed to complete paralysis by 14-18 weeks. MBP levels in the CSF became strikingly elevated to 100-1000 times the normal value. Subsequent, experiments in which rabbits were serially assessed for MBP levels demonstrated a transient elevation, which corresponded to the transient paresis, followed by dramatic elevations concurrent with the onset of paralysis. Magnetic resonance imaging (MRI) of the irradiated spinal cord showed a geographically distinct region of abnormality that corresponded to the radiation field. Histopathology demonstrated demyelination, focal astrocytosis, erythrodiapedesis, and perineuronal edema in the irradiated sections. It appears that MBP levels in the CSF reflect not only radiation-induced myelopathy but also transient demyelination, and that MRI may have the potential to indicate the region of damage.
Animals↗
Self-regulation training in sport and work.
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Competitive Behavior↗
Glucose and synaptosomal glutamate metabolism: studies with [15N]glutamate.
The metabolism of [15N]glutamate was studied with gas chromatography-mass spectrometry in rat brain synaptosomes incubated with and without glucose. [15N]Glutamate was taken up rapidly by the preparation, reaching a steady-state level in less than 5 min. 15N was incorporated predominantly into aspartate and, to a much lesser extent, into gamma-aminobutyrate. The amount of [15N]ammonia formed was very small, and the enrichment of 15N in alanine and glutamine was below the level of detection. Omission of glucose substantially increased the rate and amount of [15N]aspartate generated. It is proposed that in synaptosomes (a) the predominant route of glutamate nitrogen disposal is through the aspartate aminotransferase reaction; (b) the aspartate aminotransferase pathway generates 2-oxoglutarate, which then serves as the metabolic fuel needed to produce ATP; (c) utilization of glutamate via transamination to aspartate is greatly accelerated when flux through the tricarboxylic acid cycle is diminished by the omission of glucose; (d) the metabolism of glutamate via glutamate dehydrogenase in intact synaptosomes is slow, most likely reflecting restriction of enzyme activity by some unknown factor(s), which suggests that the glutamate dehydrogenase reaction may not be near equilibrium in neurons; and (e) the activities of alanine aminotransferase and glutamine synthetase in synaptosomes are very low.
Amino Acids↗
Interactions of benztropine, atropine and ketamine with veratridine-activated sodium channels: effects on membrane depolarization, K+-efflux and neurotransmitter amino acid release.
1. The effect of benztropine, atropine and ketamine on veratridine-induced efflux of K+, membrane depolarization and release of amino acid neurotransmitters was investigated in the preparation of rat brain synaptosomes. 2. All three drugs inhibited in a concentration-dependent manner the processes measured: the most effective compound was benztropine which exhibited an approximate Kd of 2 microM. The inhibition was not competitive in nature. 3. The veratridine titration curves in the presence of drugs were sigmoid with Hill coefficients of about 1.4. 4. At higher concentrations, benztropine, atropine and ketamine blocked uptake of amino acid neurotransmitters into synaptosomes. 5. It is postulated that benztropine, atropine and ketamine interfere with the veratridine-activated influx of sodium into synaptosomes through voltage-dependent channels by acting at the same site as local anaesthetics. Interactions at this site alter allosterically binding and action of veratridine. In addition, at higher concentrations the drugs interact with the carrier proteins for amino acid neurotransmitters and block their transport.
Amino Acids↗
Lower-extremity venous thrombosis: comparison of venography, impedance plethysmography, and intravenous manometry.
This study was undertaken to compare impedance plethysmography with lower-extremity venography and venous manometry in the diagnosis of acute deep venous thrombosis (DVT) of the lower extremity. Ninety-six extremities were studied. In this population, in which the prevalence of acute DVT was 43.8%, plethysmography had a sensitivity of 86.8% and a specificity of 72.0%. The predictive value of abnormal findings at plethysmography was 70.2%, and the predictive value of normal findings at plethysmography was 87.8%. Venous manometry was performed successfully in 89 extremities. A statistically significant difference was shown in the mean intravenous pressure between patients with and without acute DVT. However, there was considerable overlap between the two populations, limiting the predictive value of impedance plethysmography in any given patient.
Adult↗
Calcium dependent regulation of catecholamine and serotonin metabolism in human neuroblastoma cells.
Three human neuroblastoma cell lines were shown to have markedly different contents of catecholamines and serotonin. Two of the cell lines (CHP-134 and IMR-5) have higher levels of dopamine and its metabolites, while CHP-404 cells have higher levels of serotonin and its metabolites. Each cell line responded to the addition of D,L-2-amino-5-phosphonovalerate, an agent which increases plasma membrane permeability to Ca2+ (Pastuszko and Wilson, 1988; with striking changes in the metabolism of the neurotransmitters. These changes were dependent on the extracellular calcium concentration and include activation of dopamine synthesis (tyrosine hydroxylase), increased levels of dihydroxyphenylacetic acid and increased formation of N-methylated dopamine derivatives. Catabolism of serotonin to 5-hydroxyindole acetic acid was inhibited while that to 5-hydroxytryptophol was stimulated. These data clearly identify several important sites for regulation of neurotransmitter metabolism by calcium. The mechanisms, direct or indirect, by which the enzyme activities are modulated by calcium remain to be established.
2-Amino-5-phosphonovalerate↗
Relative selectivity of some conformationally constrained tryptamine analogs at 5-HT1, 5-HT1A and 5-HT2 recognition sites.
In an attempt to define pharmacophoric differences between 5-HT1, 5-HT1A and 5-HT2 recognition sites, a number of rigid analogs were studied and compared to analogous free chain tryptamines. Racemic partial ergolines RU 27849 and RU 28306 showed reduced potency at all 5-HT1 sites, but were at least equipotent to analogous tryptamines at the 5-HT2 site. A nonergoline-like constrained analog of tryptamine was similar in potency to RU 27849 at all 5-HT1 sites, but showed a 4-fold enhancement in potency over RU 27849 and tryptamine at the 5-HT2 site. At all 3 sites, 3-(tetrahydropyridyl) indoles (unless substituted at the indole 2-position) were the most potent rigid analogs studied and represent the most promising class for the development of selective compounds.
Animals↗
Amino acid neurotransmitters in the CNS. Relationships between net uptake and exchange in rat brain synaptosomes.
Carefully isolated, metabolically competent rat brain synaptosomes accumulate acidic amino acid neurotransmitters down to very low external levels. This supports the suggestion that nerve endings are involved in terminating transmission at the synapses and in maintaining low levels of these molecules in the external environment in the brain. At saturating levels of acidic amino acids, the rate of inward and outward movements of the Na+-amino acid complex (exchange) is much faster than the net uptake. The transmembrane gradients of aspartate and glutamate approach each other under all conditions explored which indicates that these two amino acids share the same transport system.
Amino Acids↗
A cholinergic antagonist, mecamylamine, blocks the phase-shifting effects of light on the circadian rhythm of locomotor activity in the golden hamster.
Despite the well known role of the light-dark cycle in the entrainment of circadian rhythms, very little is known about the neurochemical events that mediate the effects of light on the mammalian circadian clock. Recent anatomical and pharmacological data support the hypothesis that acetylcholine may be involved in relaying light-dark information from the retina to, or within, the circadian clock of rodents. If acetylcholine is required for this response, it should be possible to block the phase-shifting effects of a light pulse by blocking cholinergic neurotransmission. To test this possibility, hamsters free-running in constant darkness received an intraventricular injection of the anticholinergic drug, mecamylamine (450 micrograms), 10 min before being exposed to a 5-min pulse of light known to induce sub-maximal phase shifts in the circadian rhythm of wheel-running behavior. Compared to vehicle-injected control animals, mecamylamine treatment blocked or reduced both the phase-advancing and phase-delaying effects of light. These results support the hypothesis that acetylcholine is involved in mediating the phase-shifting effects of light on the mammalian circadian clock.
Animals↗
Effects of dietary fish oil on lung phospholipid fatty acid composition and intrinsic pulmonary vascular reactivity.
A fish oil diet has been shown to lower systemic blood pressure in man and alter vascular reactivity to exogenous noradrenaline in man and rats. The effects of a fish oil diet on the vascular reactivity of the pulmonary circulation have not been assessed. The effect of dietary lipid composition on pulmonary artery pressure and vascular reactivity of 30 adult male Sprague-Dawley rats (250-300 g) was assessed in vivo (n = 9) and in the isolated perfused lung (n = 21). Isocaloric diets containing 20% lipid (% by weight) as fish oil, corn oil, or lard were given in unlimited quantities to the rats. After one month of the diet, pulmonary vascular reactivity to angiotensin II (0.15 micrograms) and hypoxia (fractional inspired oxygen 0.025) were assessed in the isolated perfused rat lung. The haemodynamic effects of the diet on resting normoxic pulmonary artery pressure (in vivo) were assessed in chloralose anaesthetised rats. The fish oil diet appreciably increased the content of eicosapentaenoic acid (C20:5) and docosahexaenoic acid (C22:6) in lung phospholipids but had no effect on pulmonary vascular reactivity. The arachidonic acid (C20:4) content of the lung was considerably decreased. Platelet counts were lower in the rats fed fish oil. The study indicates that a fish oil diet does not alter acute intrinsic pulmonary vascular reactivity despite pronounced changes in lung phospholipid fatty acid profile.
Animals↗
Ammonia-induced release of neurotransmitters from rat brain synaptosomes: differences between the effects on amines and amino acids.
The effect of NH4Cl on release of amine and amino acid transmitters from rat brain synaptosomes was investigated. Ammonia (0.1-10 mM) stimulated the secretion of dopamine and 5-hydroxytryptamine in a dose-dependent manner, in a process which was additive with the effect of 40 mM K+, almost unaffected by withdrawal of Ca2+, and markedly decreased by increasing [H+] in the medium. The NH4Cl-induced dopamine efflux, in contrast to that caused by high [K+]e, was inhibited by benztropine. The release of gamma-aminobutyric acid, aspartate, and glutamate was unaltered by [NH4Cl] less than 5 mM, but somewhat stimulated at higher levels. Transmembrane pH gradient, acid inside, was dissipated by NH4Cl in a concentration-dependent manner and the internal alkalinization correlated with the stimulation of the rate of dopamine efflux. Transmembrane electrical potential was unaffected by [ammonia] less than 5 mM, but a small depolarization was observed at higher levels. It is postulated that ammonia-induced alkalinization of the intrasynaptic storage granules causes extrusion of amines into the cytoplasm and their subsequent leakage into the medium through a reversal of the plasma membrane transporters. A lack of correlation between the release of amino acid neurotransmitters and the dissipation of the delta pH suggests that in rat brain intrasynaptic vesicles, acidic inside, are unlikely to store substantial amounts of gamma-aminobutyric acid, aspartate, or glutamate.
Amines↗
Targeting of ganglioside GD2 monoclonal antibody to neuroblastoma.
The biodistribution of 3F8, and IgG3 murine monoclonal antibody (MoAb) specific for the disialoganglioside GD2, was studied in nude mice xenografted with human neuroblastoma (NB). 3F8 conjugated to radioactive iodine and injected intravenously localized selectively to seven human NB when compared with Ewing's sarcoma and Hela cell xenograft controls. Uptake in NB was shown to be specific for MoAb 3F8 when contrasted with pooled mouse IgG or irrelevant IgG3 MoAb controls. Both small (50 mg) and large tumors greater than 2 g) showed radiolocalization. The percent injected dose uptake per gram tumor ranged from 8 to 50% and was inversely correlated with tumor size. Optimal tumor to normal tissue ratios were reached by 24-48 hr. There was no abnormal uptake in the reticuloendothelial system and the MoAb did not cross the blood-brain barrier. Based on the kinetics of the amount of radioactivity deposited in tissues, the relative radiation dose to normal organs was estimated to be 1% to 20% of the tumor dose. The MoAb 3F8 is useful for targeting radioactivity to human NB in vivo and the nude mice xenograft model may allow optimization of parameters that influence such biodistribution.
Animals↗
The effect of thioridazine on haloperidol induced behavioral hypersensitivity.
Behavioral Hypersensitivity (BH) to dopamine agonists occurs following chronic treatment with most neuroleptics including haloperidol. In the present study we observed that the concurrent administration of thioridazine and haloperidol prevented the development of BH. In contrast, another neuroleptic, fluphenazine, coadministered with haloperidol, potentiated the degree of BH relative to animals treated with haloperidol only. In rats already made hypersensitive by chronic treatment with haloperidol, a 4 week subsequent treatment with normal saline, thioridazine alone of thioridazine in combination with haloperidol, produced normal behavioral responsiveness. These results suggest that thioridazine prevents the development of BH and can reverse the expression of haloperidol-induced BH.
Animals↗