[Analysis of the health risks in the workplace. Contribution of the work hygienist].
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Data Interpretation, Statistical↗
Biomedical subjects
S Mann
Publications and source records attributed to S Mann.
Intraneuronal ApoE in human visual cortical areas reflects the staging of Alzheimer disease pathology.
Alzheimer disease (AD) is marked by progressive loss of cortical neurons with associated cognitive decline. Multiple genetic and environmental factors likely contribute to this progressive loss. Such genetic factors include the polymorphic locus (APOE) that encodes apolipoprotein E (apoE). In order to investigate a possible correspondence between cellular localization of apoE and the neuropathology of AD, we examined the distribution of apoE-immunoreactive neurons in visual cortical areas with different apparent susceptibility to AD neuropathology (areas 17-primary sensory, 18-secondary sensory, and inferior temporal-association cortex) at different stages of AD pathology as described by Braak and Braak. We found that intraneuronal apoE was present at all these stages, however, only in visual cortical regions known to be vulnerable to AD. In the late stages, the laminar distribution of apoE-immunoreactivity matched the distribution of other markers of AD pathology, especially modified tau. These data support previous findings that intraneuronal apoE in neocortex is common in aged, nondemented controls and demonstrate that it may be more common in regions at risk for AD pathology. Thus, intraneuronal accumulation of apoE may be an attribute of cortical neurons that are more vulnerable to age-related injury with the presence of apoE antedating the classical indices of late-onset AD pathology.
Aged↗
Vitamin B-6 normalizes the altered sulfur amino acid status of rats fed diets containing pharmacological levels of niacin without reducing niacin's hypolipidemic effects.
Niacin (nicotinic acid) in large doses (> 2 g) has been increasingly the choice of lipid-lowering agent by clinicians. However, the potential risks of the use of high doses of the vitamin have not been critically considered in the same way as has the use of other lipid-lowering drugs. The present study provides evidence that pharmacological levels of niacin interfere with the metabolism of methionine, leading to hyperhomocysteinemia and hypocysteinemia. Male Sprague-Dawley rats were fed a semisynthetic diet supplemented with either 400 or 4000 mg niacin/kg (compared with 47 mg/kg diet in the control diet). In Experiment 1, feeding these diets for 3 wk resulted in a dose-related increase in the plasma and urine methionine concentrations while cysteine levels were decreased. This altered methionine metabolism was accompanied by a lower plasma vitamin B-6 concentration in niacin-supplemented rats compared with controls. In Experiment 2, the methionine and cysteine levels in plasma and urine were normalized when vitamin B-6 (10 mg/kg diet) was added to the diet containing 4000 mg niacin/kg and fed for 6 wk. This experiment also showed that plasma and urine homocysteine concentrations were increased by niacin and normalized by vitamin B-6. The hypolipidemic action of niacin was unaffected by the presence of vitamin B-6. These results indicate that niacin at large dosages interferes with methionine metabolism by affecting vitamin B-6 status. The treatment of dyslipidemia with simultaneous administration of niacin and vitamin B-6 could be a better therapy than the use of niacin alone.
Animals↗
CD30 (Ki-1)-positive primary cutaneous T-cell lymphoma: report of spontaneous resolution.
A 28-year-old man in whom CD50 (Ki-1)-positive cutaneous large cell lymphoma manifested as multiple widespread ulcerated nodules; which developed over a 2-week period, is reported. The lymphoma was composed of large anaplastic cells in large clusters, with scattered eosinophils, neutrophils and small lymphocytes. Extensive staging investigations revealed no extra-cutaneous disease. No treatment was given because, within weeks of presentation, the nodules began to regress spontaneously and the patient remains disease-free 20 months later.
Adult↗
Curriculum collaboration and the Ottawa Charter: a nursing initiative.
The World Health Organization (WHO) and the International Council of Nurses (ICN) have been consistent in their call for nurses to be involved with Primary Health Care (PHC). This paper will demonstrate how an innovative partnership between the School of Nursing, Flinders University of South Australia (FUSA) and Noarlunga Health Services (NHS) has been instrumental in developing an undergraduate nursing curriculum which has the potential to guide future nursing practice. The Community Enrichment Project (CEP) has been an example of health promotion in practice and demonstrates how a PHC philosophy can permeate all levels of health care.
Community Health Nursing↗
The biomimetics of enamel: a paradigm for organized biomaterials synthesis.
The formation of enamel takes place through a sequence of processes that can be mimicked in inorganic materials chemistry. This chapter describes the generic features of enamel biomineralization in terms of a house-building analogy. Four stages are identified: supramolecular preorganization and spatial patterning; interfacial molecular recognition in inorganic nucleation; vectorial crystallization; and pattern evolution and hierarchy. Each of these concepts can be translated into synthetic approaches to the formation of inorganic materials with organized architectures. An example of applying this biomimetic paradigm is described. Supersaturated water-in-oil microemulsions have been used to synthesize microskeletal calcium phosphates by controlled nucleation and vectorial growth in constrained reaction environments. The results of these preliminary studies suggest that biomimetic concepts could be useful in the fabrication of biomaterial implants with controlled porosity and microstructure.
Amelogenesis↗
Immunomagnetic isolation of magnetoferritin-labeled cells in a modified ferrograph.
Pan T, helper, and cytotoxic lymphocytes were isolated from the human peripheral blood mononuclear cell fraction by antibody staining, ferritin labeling, and deposition on glass slides. Two distinct forms of ferritin were used: one was native horse spleen ferritin, and the other was magnetoferritin. Magnetoferritin was obtained by reconstituting the horse spleen ferritin iron core with superparamagnetic magnetite instead of the usual paramagnetic ferrihydrite crystal. The cell deposition on microscopic glass slides in the magnetic field was obtained by an instrument that was adapted from an industrial magnetic deposition analyzer, the ferrograph. The identity of cells in the magnetic deposits was confirmed by comparing the cell fractions in the feed and in the eluate with the use of flow cytometry. The immunostaining protocol amplified the number of ferritin molecules per cell surface antigen 20-70 times. Magnetoferritin, but not native ferritin, imparted a sufficient magnetic moment to cells to deplete the labeled cell population between 67 and 88% of its initial concentration in a magnetic field of 1.67 Tesla (T), a field gradient of 2.57 T/mm, and a flow rate of 0.01 ml/min. This study showed that the magnetic moment of magnetoferritin was sufficient for immunomagnetic isolation of lymphocytes from mononuclear cell preparations in the modified ferrograph.
Animals↗
Agrin is synthesized by retinal cells and colocalizes with gephyrin [corrected].
At the neuromuscular junction, motoneuron-derived agrin is concentrated in the basal lamina of the synaptic cleft where it is responsible for the formation of the postsynaptic apparatus. As a step toward understanding agrin's role in the developing central nervous system, we have characterized agrin in retinal cell cultures as well as in the intact retina. Agrin was synthesized and secreted by cultured retinal cells and at least part of this agrin was active in acetylcholine receptor aggregation. Punctate anti-agrin immunoreactivity was associated with the cell bodies and processes of retinal neurons. Double labeling with antibodies against agrin and against the synapse-associated molecule gephyrin demonstrated that approximately half of the gephyrin clusters colocalized with the punctate agrin immunoreactivity in vitro. In the in vivo retina, more than 80% of the gephyrin clusters colocalized with extracellular agrin. These data indicate that agrin is concentrated at synapses in the retina as it is at the neuromuscular junction.
Agrin↗
A physiologically based pharmacokinetic model for arsenic exposure. I. Development in hamsters and rabbits.
A physiologically based pharmacokinetic model for exposure to inorganic arsenic in hamsters and rabbits has been developed. The model in its present state simulates three routes of exposure to inorganic arsenic: oral intake, intravenous injection, and intratracheal instillation. It describes the tissue concentrations and the urinary and fecal excretions of the four arsenic metabolites: inorganic As(III) and As(V), methylarsonic acid, and dimethylarsinic acid. The model consists of five tissue compartments, chosen according to arsenic affinities: liver, kidneys, lungs, skin, and others. The model is based on physiological parameters, which were scaled according to body weight. When physiological parameters were not available, the data for the model were obtained by fitting (tissue affinity, absorption rate, and metabolic rate constants). The excretions of the arsenic metabolites in urine and feces are well simulated with the model for both species. Further validation of the arsenic metabolite concentrations in the tissues and in vitro measurements of the tissue affinity constants are discussed.
Administration, Oral↗
A physiologically based pharmacokinetic model for arsenic exposure. II. Validation and application in humans.
A physiologically based pharmacokinetic model (PB-PK) for inorganic arsenic exposure in humans has been developed. This model is an extension of a PB-PK model for hamsters and rabbits, with adjustments for body weight, metabolic rates, and absorption rates. It describes the absorption, distribution, metabolism, and excretion of arsenate, arsenite (As(III)), methyl arsonate, and dimethyl arsinate, the four major metabolites of inorganic arsenic. The routes of intake considered are inhalation of arsenic dust and fumes and oral intake of arsenic via drinking water and food. The PB-PK model for the oral exposure route is validated using data on urinary excretion after repeated oral exposure to As(III) as well as after exposure to inorganic As via drinking water. Absorption by inhalation is validated using data on urinary excretion after occupational exposure to arsenic trioxide dust and fumes. In both cases, the model gives satisfactory results for urinary excretion of the four As metabolites. The PB-PK model is also used in the description of the effects on the kinetics of exposure via different routes and for the simulation of various realistic exposure scenarios.
Administration, Inhalation↗
Biochemical and functional characterization of basal lamina-bound agrin in the chick central nervous system.
Agrin is a high-molecular weight extracellular matrix molecule, initially purified from the electric organ of the marine ray Torpedo californica, which induces on the surface of cultured myotubes the formation of postsynaptic specializations similar to those found at the neuromuscular junction. Agrin immunoreactivity is highly concentrated in the basal lamina of the synaptic cleft but is also found in a number of other tissues where its function is not known. We characterized agrin associated with two basal laminae from the central nervous system, the inner limiting membrane of the retina and the mesencephalic external limiting membrane. A major broad band with an apparent molecular weight of > 300 kDa was identified in immunoblots of isolated basal laminae from retina, mesencephalon, kidney and muscle, showing that basal lamina-bound agrin from the central nervous system and that from non-neural tissues have similar molecular sizes. Agrin is stably but not covalently bound to the inner limiting membrane and could be completely removed only with strong detergents. Agrin could be partially extracted with buffers that are also able to partially release acetylcholine receptor aggregation activity from the neuromuscular junction or from the electric organ. Despite these immunological and biochemical similarities, agrin from both central nervous system-derived basal laminae was not able to induce acetylcholine receptor aggregation on cultured myotubes. This shows that functionally different agrin isoforms are associated with basal laminae in the central nervous system compared to the neuromuscular junction or the electric organ.
Agrin↗
Valproic acid treatment of learning disorder and severely epileptiform EEG without clinical seizures.
Using a single-patient (n = 1) clinical trial, we studied a 7-year-old boy who presented with unsatisfactory progress in school and whose electroencephalogram had very active independent frontal spike discharges. He had not had clinical seizures. The patient was randomized to receive valproic acid, 125 mg twice daily, (four periods) or matching placebo (four periods) over 8 weeks. Primary endpoints were the Wechsler Intelligence Scale for Children-Revised Coding sub-test and a handwriting sample. Behavior was monitored using teacher's and parent's Conners questionnaires. His score on the Wechsler Intelligence Scale for Children-Revised Coding subtest was significantly improved while he was taking valproic acid (P = .03). His electroencephalogram improved from a pretreatment recording of 28 spike discharges per minute to a normal recording while on valproic acid. We conclude that in this patient, valproic acid had a cognitive enhancing effect, probably by reducing epileptiform discharges.
Anticonvulsants↗
Outcome of high-dose therapy and autologous transplantation in non-Hodgkin's lymphoma based on the presence of tumor in the marrow or infused hematopoietic harvest.
PURPOSE: To evaluate the outcomes in 65 consecutive patients with non-Hodgkin's lymphoma (NHL) undergoing high-dose therapy (HDT) and autologous transplantation based on initial marrow involvement and the presence or absence of minimal disease in the hematopoietic harvests. PATIENTS AND METHODS: Patients with any history of histologic evidence of marrow tumor underwent autologous peripheral-blood stem-cell transplantation (PSCT), whereas others underwent autologous bone marrow transplantation (ABMT). Patients who underwent ABMT were further segregated retrospectively into two groups depending on whether there was evidence by cell culture and/or Southern analysis of minimal tumor in the marrow harvest. RESULTS: Comparable proportions (58% to 60%) of patients in each of the two groups (PSCT and ABMT) achieved a complete clinical remission (CR) at 100 days. For patients who achieve a CR, the actuarial relapse-free survival rate at 5 years for PSCT patients who received a tumor-negative apheresis harvest was 64%, compared with 57% for patients who received a tumor-negative bone marrow harvest and 17% for patients who received a histologically negative but minimally contaminated bone marrow harvest. Lymphoma grade and phenotype were not significant predictors of outcome. CONCLUSION: The observation that survival was significantly better in the groups of patients who received tumor-negative harvests and worse for patients who received minimally contaminated harvests suggests that tumor cells, even at minimal levels, reinfused in the transplanted harvest are responsible for progression in a proportion of patients who achieve a CR following HDT, although other biologic characteristics of the tumor could also be important. A relatively good outcome can be achieved with HDT and PSCT, even in patients with a significant marrow tumor burden.
Adolescent↗
[General automated documentation and performance data on the surgical intensive care unit--the theoretical concept of the Regensburg Surgical University Clinic].
Documentation is becoming an ever more time-consuming task due to the need to document increasing ICU productivity, quality management and cost-assessment data. Automatic charting of on-line monitoring data, therapeutic-device data, clinical laboratory data, microbiological data, radiological data and other data reduces documentation time significantly. One of the major advantages of PDMS in the SICU is the quality of the documentation and with better documentation the therapist is able to improve the quality of care. Not only the physician, but also nurses and physiotherapists are able to benefit from these advantages. Our concept, SURGIC (Department of Surgery, University Regensburg, Germany, Intensive Care), stands for: widely automated documentation, work orientation, including physicians, nurses' and physiotherapists' tasks, minimal dataset for simple use and perfect overview, costs assessments, scientific dataset, SICU PDMS as a part of the clinical information system, and professional support by a software-house is necessary.
Computer Systems↗
Rethinking sexual health clinics. Improved communication and referral process may be a better use of resources.
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Communication↗
Classical and quantum magnetic phenomena in natural and artificial ferritin proteins.
Artificial ferritin has been synthesized with control of both the magnetic state (antiferromagnetic or ferrimagnetic) and the particle size over an ofer of magnitude in the number of iron atoms. The magnetic properties of the artificial ferritin were compared with those of natural horse spleen ferritin in a range of temperatures (20 millikelvin to 300 kelvin) and fields (1 nanotesla to 27 tesla). In the classical regime, the blocking temperature was found to correlate with the average particle size. A correlation was also observed in the quantum regime between the resonance frequency of macroscopic quantum tunneling of the Néel vector and the particle size. At high magnetic fields (to 27 tesla), a spin flop transition with a strong dependence on orientation was seen in the natural ferritin, providing evidence of antiferromagnetism in this system.
Animals↗
Reconstitution of manganese oxide cores in horse spleen and recombinant ferritins.
The formation of Mn(III) oxyhydroxide (MnOOH) cores within the nanoscale cavity of the iron storage protein ferritin has been investigated by electron microscopy and visible absorption spectroscopy. At pH 8.9, discrete amorphous MnOOH cores were formed within horse spleen apoferritin at a range of metal:protein ratios, as well as in ferritin molecules seeded with a small ferrihydrite nucleus. Analysis of the resultant core size distributions showed that the reconstitution of horse spleen apoferritin with Mn(II) was similar to that observed previously for Fe(II) reconstitution in recombinant human L-chain ferritin, suggesting that horse spleen apoferritin does not exhibit Mn(II) oxidase activity at pH 8.9. Reconstitution with MnOOH shows essentially "all-or-nothing" behavior in which many protein molecules remain unmineralized whilst others are loaded to maximum capacity. Kinetic studies showed no significant differences between horse spleen ferritin, recombinant H- and L-chain homopolymers, and H-chain variants containing site-directed modifications at the ferroxidase and putative Fe nucleation centers. Our results indicate that the reconstitution of ferritin with MnOOH cores proceeds by a nonspecific pathway. We propose that the outer surface of the protein inhibits the development of MnOOH nuclei in bulk solution whereas the inner surface is inactive, enabling nucleation and growth to proceed unperturbed within the cavity. One possibility is that differences in the general polyelectrolyte properties of these two surfaces, rather than site-specific charges, account for the "Janus" behavior of the molecule. A similar mechanism might also increase the specificity of iron oxide mineralization in ferritins that lack ferroxidase centers.
Animals↗