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The performance of a personal neutron dosemeter with a single silicon diode using a linear combination of its pulse height information was studied. Its dosimetric behaviour in fields with neutrons of different energy and directional distribution is shown for neutron energies ranging from thermal to 100 MeV and for directions of incidence ranging from frontal to lateral. The dosemeter is photon-insensitive and its dose detection threshold is at about 20 microSv. The dosimetric characteristics are compared with those of commercial dosemeters based on silicon detectors.
In nuclear medicine departments, where radioactive sources are manipulated, the personnel can receive large radiation doses to the skin of their hands. For performing detailed characterisations and dose optimisations of these workplaces, active extremity dosemeters can be used as complementary tools to passive hand monitoring. Active extremity dosimetry is still a subject of research. In this context, IRSN has started a research and development programme. As a first step, a hospital workplace study has been performed using thermoluminescence dosemeters and has shown, in agreement with previous works, that the pads of the fingers, points that are very difficult to instrument, receive the largest doses. Numerical studies have now started, with the aim of calculating the dose equivalent gradients through the hands, in order to optimise the locations of the detectors.
The present article describes the conduct of clinical psychiatric research in this highly sophisticated age of multidisciplinary investigations and long-term follow-ups. Planning proceeds in stages from initial discussions to statistical analysis. Observations and descriptions constitute the primary stuff from which conclusions may be obtained. However, the entire program needs sufficient flexibility to enable the original plan to be altered by additions, alterations, or deletions without harming the primary purposes. The contents are hardly new, but they need constant repetition. In fact we seem to have made little dent in a field redundant with reductionism and unanswerable questions. Objective ad subjective methods are increasingly becoming fused instead of being in conflict. Bit by bit, the planning continues throughout any research program which is varyingly exciting, boring, and again exciting, and some answers become apparent if not complete.
Microsomal enzyme inducers are capable of modulating biliary excretion of organic anions and bile flow, but the mechanism for modulation is unknown. Therefore, this study was designed (1) to determine the effects of microsomal enzyme inducers on protein and mRNA expression of rat multidrug resistance protein 2 (Mrp2), a canalicular organic anion transporter; and (2) to determine whether classes of microsomal enzyme inducers affect Mrp2 expression in similar manners, thus implying specific nuclear receptor-activated transcription pathways. Male Sprague-Dawley rats were treated with aryl hydrocarbon (Ah) receptor (AhR) ligands/cytochrome P450 (CYP) 1A inducers, constitutive androstane receptor (CAR) ligands/CYP2B inducers, pregnane-X receptor (PXR) ligands/CYP3A inducers, peroxisomal proliferator-activating receptor-alpha (PPARalpha) ligands/CYP4A inducers, antioxidant/electrophile response element (ARE/EpRE) ligands, CYP2E1 inducers, or control vehicle. Mrp2 protein levels were significantly increased by all 3 PXR ligands/CYP3A inducers (pregnenolone-16alpha-carbonitrile [PCN], spironolactone [SP], and dexamethasone [DEX]) and by both ARE/EpRE ligands (ethoxyquin [EQ] and oltipraz [OPZ]). In contrast, PPARalpha ligands/CYP4A inducers (clofibric acid [CLOF], di-(2-ethylhexyl)phthalate [DEHP], and perfluorodecanoic acid [PFDA]) tended to decrease Mrp2 protein levels. Mrp2 mRNA expression was not significantly affected by any microsomal enzyme inducer, though ARE/EpRE ligands tended to upregulate Mrp2 mRNA. In summary, this study demonstrates that Mrp2 protein levels are significantly increased by PXR ligands/CYP3A inducers and ARE/EpRE ligands, and appear to be decreased by PPARalpha ligands/CYP4A inducers by posttranscriptional mechanisms. Furthermore, these data suggest that measuring Mrp2 mRNA is not a good indicator for Mrp2 protein expression in vivo.
Protein kinases represent a diverse family of enzymes that play critical roles in regulation. The simplest and best-understood biochemically is the catalytic (C) subunit of cAMP-dependent protein kinase, which can serve as a framework for the entire family. The amino-terminal portion of the C subunit constitutes a nucleotide binding site based on affinity labeling, labeling of lysines, and a conserved triad of glycines. The region beyond this nucleotide fold also contains essential residues. Modification of Asp 184 with a hydrophobic carbodiimide leads to inactivation, and this residue may function as a general base in catalysis. Despite the diversity of the kinase family, all share a homologous catalytic core, and the residues essential for nucleotide binding or catalysis in the C subunit are invariant in every protein kinase. Affinity labeling and intersubunit cross-linking have localized a portion of the peptide binding site, and this region is variable in the kinase family. The crystal structure of the C subunit also is being solved. The C subunit is maintained in its inactive state by forming a holoenzyme complex with an inhibitory regulatory (R) subunit. This R subunit has a well-defined domain structure that includes two tandem cAMP binding domains at the carboxy-terminus, each of which is homologous to the catabolite gene activator protein in Escherichia coli. Affinity labeling with 8N3 cAMP has identified residues that are in close proximity to the cAMP binding sites and is consistent with models of the cAMP binding sites based on the coordinates of the CAP crystal structure. An expression vector was constructed for the RI subunit and several mutations have been introduced. These mutations address 1) the major site of photoaffinity labeling, 2) a conserved arginine in the cAMP binding site, and 3) the consequences of deleting the entire second cAMP binding domain.
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BACKGROUND: Combining a hypnotic and an analgesic to produce sedation, analgesia, and surgical immobility required for clinical anesthesia is more common than administration of a volatile anesthetic alone. The aim of this study was to apply response surface methods to characterize the interactions between remifentanil and sevoflurane. METHODS: Sixteen adult volunteers received a target-controlled infusion of remifentanil (0-15 ng/ml) and inhaled sevoflurane (0-6 vol%) at various target concentration pairs. After reaching pseudo-steady state drug levels, the Observer's Assessment of Alertness/Sedation score and response to a series of randomly applied experimental pain stimuli (pressure algometry, electrical tetany, and thermal stimulation) were observed for each target concentration pair. Response surface pharmacodynamic interaction models were built using the pooled data for sedation and analgesic endpoints. Using computer simulation, the pharmacodynamic interaction models were combined with previously reported pharmacokinetic models to identify the combination of remifentanil and sevoflurane that yielded the fastest recovery (Observer's Assessment of Alertness/Sedation score > or = 4) for anesthetics lasting 30-900 min. RESULTS: Remifentanil synergistically decreased the amount of sevoflurane necessary to produce sedation and analgesia. Simulations revealed that as the duration of the procedure increased, faster recovery was produced by concentration target pairs containing higher amounts of remifentanil. This trend plateaued at a combination of 0.75 vol% sevoflurane and 6.2 ng/ml remifentanil. CONCLUSION: Response surface analyses demonstrate a synergistic interaction between remifentanil and sevoflurane for sedation and all analgesic endpoints.
Current economic and demographic trends in the United States indicate the demand for complex treatments, such as infusion therapies at home, will continue to escalate. In light of the increasingly acute and autonomous nature of home health practice, examination of home care nursing process affecting patient care outcomes is crucial. This study explored the cognitive, technical, and interpersonal components included in total parenteral nutrition (TPN) home care nursing. The purpose of this study was to evaluate psychometrically the Schmele Instrument to Measure the Process of Nursing Practice in Home Health (SIMP-H) so that it may be used to examine high-tech home care nursing process. Home visits must be observed to identify the specific cognitive, technical, and interpersonal components included in high-tech home care nursing that are important for patient care outcomes. This study captured high-tech home care nursing process on videotape, which provided a medium for evaluating interobserver reliability for the SIMP-H. Results revealed an interobserver reliability coefficient of .72.
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High-density event-related potentials (HD-ERPs) were recorded while adults passively viewed colour images of faces that artificially (Experiment I) or naturally (Experiment II) differed in configuration. In Experiment I, altering features of faces to make them less typical and less attractive did not affect the amplitude of N170, but did affect the amplitude of P1 and P2. In Experiment II, the P1 and N170 were larger for unattractive and atypical faces compared with attractive and typical faces, in the absence of P2 effects. The results show for the first time that variations in facial configuration modulate ERP activity as early as P1, but that modulation of later latency components depends on the nature of the stimuli and implicit task demands.
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OBJECTIVE: To gain molecular insights into different HIV-1 strains present in two different states of India, nucleotide sequences derived from the env region of four HIV-1 strains were analysed. DESIGN: HIV-1 was isolated from high-risk patients from the states of Maharashtra (city of Bombay) and Goa. The molecular analysis of the env region encompassed all variable domains of the external glycoprotein, gp120. METHODS: Genomic DNA from cultured cells infected with each of the four Indian HIV-1 strains independently was amplified by polymerase chain reaction (PCR). PCR fragments were cloned and sequenced and a phylogenetic tree constructed. RESULTS: All four Indian HIV-1 sequences were closely related to each other. The closest related sequence to them was from a South African isolate, HIV-1NOF, with a homology of 85-87%. In the phylogenetic tree, the Indian and the South African HIV-1 sequences cluster together and constitute a subtype different from the North American/European, Central African, Uganda/Rwanda and Northern Thailand subtypes. Interestingly, the viruses of this subtype are characterized by an additional potential N-glycosylation site C-terminal to the CD4-binding domain. CONCLUSION: The low variation between the HIV-1 sequences from randomly chosen individuals from high-risk cohorts in two Indian states suggests a rapid and recent spread of HIV and, possibly, introduction of the virus by the same route, most probably heterosexual transmission. The rapid spread of HIV-1 variants in India, which form a subgroup of their own together with a South African strain, necessitate consideration of these strains in vaccine development.